Biomedical subjects

M I Ross

Publications and source records attributed to M I Ross.

At least 91 records · Page 5Linked to original sources

PubMed1995

Adjuvant radiation therapy after axillary lymphadenectomy for metastatic melanoma: toxicity and local control.

BACKGROUND: Certain patients with locally advanced melanoma have a high risk of regional recurrence after surgical excision and lymphadenectomy alone. Growing evidence suggests that radiation therapy may improve local control with acceptable morbidity for patients with melanoma in some sites. There is no information regarding the safety or efficacy of this treatment when applied to the axilla for regional metastasis of cutaneous melanoma. METHODS: We conducted a retrospective evaluation of patients who received postoperative radiation therapy to the axillary lymphatics for malignant melanoma at the M. D. Anderson Cancer Center between 1980 and 1992. Twenty-eight patients were identified who had undergone a formal axillary lymph node dissection followed by postoperative irradiation to the full axilla and supraclavicular fossa. Twenty-two patients were irradiated using a hypofractionated treatment regimen (4-7 Gy/fraction), generally to 30 Gy in five fractions. RESULTS: Sixteen patients are currently alive. Actuarial survival at 5 years is 50.1%. Local tumor recurred or persisted in five patients, four of whom had clinically palpable tumor when they were irradiated. CONCLUSIONS: Postoperative irradiation of the axilla for malignant melanoma has acceptable toxicity, even in those with extensive axillary dissection. In this group, patients treated for subclinical disease had a low rate of recurrence (1 of 21, [5%]).

Actuarial Analysis↗

PubMed1995

Tetramodality treatment of human melanoma in vitro.

We evaluated the in vitro cytotoxic effects of combined human tumour necrosis factor alpha (TNF), human interferon gamma (IFN-gamma), melphalan (L-PAM) and hyperthermia (HTX) on human melanoma cell lines using the crystal violet assay. HTX (40 degrees C, 1 h) alone had no effect. The responses of the cell lines to TNF were in the rank order of 939 cells > 987 > 284 > C8161 > 852 > A2058 approximately 0, and all displayed shallow dose-response curves; no significant thermal enhancement of TNF cytotoxicity was apparent with this heat dose. All cell lines were sensitive to L-PAM, with 284 cells being the most sensitive; HTX caused only slightly increased sensitization to L-PAM. The combination of TNF and L-PAM resulted in generally subadditive or additive cytotoxicity, with or without HTX. The response to IFN-gamma alone was heterogeneous; the 939, 284 and 852 cell lines were sensitive to a dose as low as 20 ng/ml, whereas the 987 line was resistant to 2.0 micrograms/ml, even with HTX. IFN-gamma enhanced the response to TNF only of the TNF-resistant A2058 cell line, but there was no enhancement of the response to L-PAM for any line. Thus, this tetramodality combination achieved generally subadditive or additive cytoxicity in vitro.

Cell Survival↗

PubMed1995

Role of computed tomography in the staging of patients with local-regional metastases of melanoma.

PURPOSE: To determine the value of computed tomographic (CT) scans in the staging of asymptomatic melanoma patients who presented with or developed local-regional disease as the first site of recurrence and had both a normal chest radiograph and serum lactate dehydrogenase (LDH) level. PATIENTS AND METHODS: The records of 99 patients with local-regional disease were reviewed. Of these, 89 met the study criteria and are the subjects of this analysis. Radiologic findings were categorized into the following four groups: (1) true-positive (TP), when the scan identified either regional or distant disease that was not appreciated on physical examination; (2) false-positive (FP), when the scan showed a radiologic abnormality that either did not change for at least 6 months or was proven to be histologically benign; (3) false-negative (FN), when a patient had symptoms suggestive of or suspicious for metastases and was subsequently found to have metastases, but all imaging studies were nondiagnostic; and (4) true-negative (TN), when all imaging studies were negative for metastases in an asymptomatic patient. RESULTS: Findings on CT scan were TP for six patients (7%), FP for 20 (22%), and TN for 63 (71%). Of the six patients with TP findings, CT of the chest identified disease that was not visible on chest radiograph in only one and CT of the abdomen or pelvis showed metastases in five. CT or magnetic resonance imaging (MRI) of the brain showed no evidence of brain metastases in any patient, although it showed asymptomatic skull metastases in one patient. The most common FP findings were hypodense hepatic lesions and noncalcified lung nodules. CONCLUSION: TP findings are observed in approximately 7% of patients with local-regional disease, which indicates a low yield but definite usefulness of CT scans in this subset of patients. Because FP are more common than TP findings, histologic diagnosis of recurrence is advisable. CT scan or MRI of the brain is not necessary in asymptomatic patients. CT of the chest adds little to a chest radiograph. In light of today's more cost-conscious health-care environment, our results are of practical importance.

Adult↗

PubMed1995

Prognostic value of size of lymph node metastases in patients with cutaneous melanoma.

PURPOSE: To determine the prognostic significance of the size of the lymph node mass as measured by physical examination (PE) and of the size of the largest node measured by pathologic analysis (path) in patients with cutaneous melanoma and nodal metastases. PATIENTS AND METHODS: The medical records of all patients with nodal metastases seen at The University of Texas M.D. Anderson Cancer Center from January 1, 1973 to December 31, 1989 were reviewed. Patient eligibility criteria included the following: (1) availability of data describing the nodal size either by PE or by path and the number of positive nodes; (2) no history of preoperative chemotherapy or radiotherapy; and (3) no history or presence of in-transit, satellite, local, or distant metastases. Eleven variables, including largest diameter of the nodal mass by PE and diameter of the largest node by path, were examined as potential prognostic factors for disease-free survival (DFS) and overall survival (OS). RESULTS: Of 800 patients evaluated, 442 met the eligibility criteria and are the subjects of this study. In the univariate analysis, size of the nodal mass by PE was marginally significant for survival as a continuous variable (P = .045), but not as a categorical variable using a cutoff size of < or = 3 or more than 3 cm as indicated by the American Joint Committee on Cancer (AJCC) staging system (P = .61). Size of the largest node by path was not significant for survival. In the multivariate analysis, only the number of positive nodes (P < .001), age (P < .001), and tumor thickness (P < .001) were significant for survival. CONCLUSION: Size of the nodal mass by PE and size of the largest node by path are not useful prognostic factors for survival and should be eliminated from the current staging system. More powerful and well-established prognostic factors, such as the number of positive nodes, should be considered for inclusion in staging.

Adult↗

PubMed1994

HLA-DQB1*0301 association with increased cutaneous melanoma risk.

Susceptibility to a variety of malignancies has been linked to human leukocyte antigen (HLA) genes, including the HLA class II allele DQB1*0301. To determine whether melanoma risk is associated with HLA class II alleles, molecular oligotyping of HLA class II-DRB1, -DQA1 and -DQB1 genes was performed for 45 patients with melanoma. The DQB1*0301 allele was present in 56% of melanoma patients vs. 27% of 200 local Caucasian controls. This difference was highly significant (Bonferroni's-corrected chi-square p = 0.003, OR = 3.4). No other class II allele tested was present at significantly increased or decreased frequency in melanoma patients. Furthermore, presence of DQB1*0301 in melanoma patients was associated with advanced disease. Melanoma patients carrying the DQB1*0301 allele presented on average with thicker primary tumors (mean 3.7 mm vs. 1.8 mm, 2-tailed p = 0.02) and were more likely to present with regional or distant metastatic disease (stages III-IV, 44% vs. 5%, chi-square p = 0.003), compared to melanoma patients without DQB1*0301. Risk of melanoma incidence or progression may be influenced by DQB1*0301 or a closely linked gene.

Alleles↗

PubMed1994

Comparison of charges related to radiotherapy for soft-tissue sarcomas treated by preoperative external-beam irradiation versus interstitial implantation.

BACKGROUND: We compared treatment-related charges associated with external beam irradiation and interstitial implantation for soft-tissue sarcoma of the extremity. METHODS: Charges related to radiotherapy in 35 patients with soft-tissue sarcoma of the extremity were reviewed. Preoperative external beam irradiation (EB) delivering 50 Gy in 25 fractions with 6 MV photons was administered to 12 of the patients evaluated. The remaining 23 patients were treated with interstitial implantation (IR) as the only radiotherapeutic intervention. The anatomic distribution of the sarcomas treated by IR included 14 lower-extremity (LE) and nine upper-extremity (UE) lesions. The average length of iridium wire used for IR was 78 cm. Because LE lesions tend to be larger, the average length equaled 109.5 cm as compared with the 47 cm for UE implants. RESULTS: The radiotherapeutic approach represented the only difference in treatment-related charges because the operative procedure of wide local excision was performed in each group. No difference in perioperative complications was observed between the two treatment approaches. Charges were stratified according to hospital-based and professional services. Radiotherapy-based hospital charges for the administration of EB averaged $6,515 compared with $4,050 for IR (p < 0.0001). Professional services also were significantly different, totaling $4,390 for EB and $3,240 for IR (p < 0.0001). The total of these charges for radiotherapy procedures and professional fees equaled $10,905 for EB compared with $7,290 for IR (p < 0.0001). Incorporating the necessary operating-room time for implant placement ($750) and five additional hospital days ($1,800), the costs associated with IR totaled $9,840; using chi-square analysis, the cost for IR remained significantly (p < 0.0001) less expensive than the $10,905 associated with EB. Because a large component of the radiotherapy cost for IR is related to the length of iridium 192 wire required, charges were stratified according to the location of the tumor. The total charge for IR of the UE equaled $9,345 compared with $10,335 for LE implants. Chi-square comparison for both UE and LE implants continued to show significant differences (p < 0.0001) when related to EB therapy. CONCLUSION: Cost-analysis comparison of brachytherapy versus external beam irradiation found lower charges for patients undergoing adjuvant irradiation with brachytherapy for soft-tissue sarcoma. To optimize the cost-benefit ratio, prospective studies are necessary to define the application of these radiotherapeutic approaches based on clinical criteria.

Arm↗

PubMed1994

The free transverse rectus abdominis musculocutaneous flap for breast reconstruction: one center's experience with 211 consecutive cases.

All patients undergoing breast reconstruction with free transverse rectus abdominis musculocutaneous (TRAM) flaps from February 1989 to November 1992 were registered into a computerized database and followed prospectively. There were 211 free TRAM flap breast reconstructions in 163 patients; 48 reconstructions were bilateral. A muscle split technique was used in 108 of 211 reconstructions (51%). Total flap loss occurred in 3 of 211 reconstructions for a success rate of 99%. Complications occurred in 81 of 211 reconstructions (38%). Fat necrosis or partial flap loss occurred in 15 of 211 (7%). Hernia or bulge occurred in 11 patients (5%). The bulge/hernia rate tended to be lower in the muscle split group (4 of 108 [4%]) than in those who did not have muscle split procedures (7 of 103 [7%]), whereas the fat necrosis rate was slightly higher in the former group (9 of 108 [8%]) than in the latter (6 of 103 [6%]). Neither difference was statistically significant. However, patients who currently or previously smoked cigarettes did have a significantly higher incidence of fat necrosis: 12 of 99 smokers (12%) had fat necrosis compared with 3 of 112 nonsmokers (3%; p = 0.02).

Adult↗

PubMed1994

Surgical management and prognostic factors in patients with subungual melanoma.

OBJECTIVE: Forty-six cases of subungual melanoma were reviewed to identify significant clinicopathologic prognostic factors, determine the role of DNA content analysis in the biologic assessment of these tumors, and evaluate the effectiveness of amputation level, lymph node dissection (LND), and regional limb perfusion on the survival of these patients. BACKGROUND: Subungual melanoma is a unique and rare subtype of melanoma, constituting only 1% to 3% of cases. Thus, little is known about prognostic factors and optimal management of patients with this disease. Moreover, the appropriate level of amputation and LND and limb perfusion in the management of subungual melanoma remain controversial. METHODS: Forty-six patients underwent amputation alone or in combination with LND and/or regional limb perfusion for primary subungual melanoma. The effects of these treatment modalities and the prognostic significance of patient and tumor-related variables, including DNA flow cytometric data, on overall survival were assessed. RESULTS: Univariate statistical analysis identified six factors that significantly affected patient survival. They were stage at diagnosis (p = 0.0001), percentage of aneuploid cells (p = 0.01), presence of ulceration (p = 0.02) or bone invasion (p = 0.02), thickness of the primary lesion (p = 0.03), and percentage of cells in S-phase (p = 0.03). Multivariate analyses identified tumor stage and S-phase fraction as independent prognostic factors in these patients. Survival did not differ among patients who received amputation alone or those who underwent amputation in combination with LND or perfusion (p = 0.90); however, the use of limb perfusion reduced the incidence of locally recurrent disease. The level of amputation did not affect patient survival (p = 0.74) or the incidence of local recurrence. CONCLUSIONS: The study identified several significant prognostic factors, including DNA flow cytometric parameters, in patients with subungual melanoma. In addition, it showed that conservative amputation of the affected digit at the level of the proximal interphalangeal or metacarpophalangeal/metatarsophalangeal joint appears to be safe, provided that clear margins are obtained. Although isolated limb perfusion may reduce the incidence of local recurrence, LND, or limb perfusion in the routine management of subungual melanoma remains controversial.

Adult↗

PubMed1994

Surgery and other local-regional modalities for all stages of melanoma.

The recommendations for the surgical management of clinically localized melanoma are now more clearly defined. Based on the results of two large randomized trials, optimal excision margins for primary tumors of varying thickness up to 4 mm have been determined: 1 cm for lesions smaller than 1 mm and 2 cm for lesions that are between 1 and 4 mm. In 90% of patients, the soft-tissue defect created by 2-cm excisions can be closed primarily, allowing surgery for early-stage melanoma to be performed predominantly on an outpatient basis. The role for an elective lymph node dissection in those patients with higher risk primary tumors is still under debate. "Selective lymphadenectomy" using lymphatic mapping and sentinel node biopsy offers a rational approach to clinically negative regional lymph node basins. The promising early results with lymphatic mapping are exciting, but need to be confirmed in a multi-institutional trial. Renewed interest has developed in hyperthermic limb perfusion for the treatment of transit and locally advanced recurrent disease because of the availability of melphalan and the recent reports of higher response rates with the addition of tumor necrosis factor and interferon gamma to melphalan. In the management of metastatic disease, recent large series have demonstrated that surgery can offer excellent palliation and, in some selected clinical settings, prolong survival. In those patients with surgically inaccessible lesions, radiation therapy can provide valuable palliation. The value of hyperthermia in addition to radiation therapy in the treatment of metastatic melanoma is still under investigation.

Chemotherapy, Cancer, Regional Perfusion↗

PubMed1994

Localization of impalpable breast masses: value of sonography in the operating room and scanning of excised specimens.

OBJECTIVE: Despite the variety of techniques available, mammographically guided preoperative localization of impalpable masses in the breast can be a difficult procedure for radiologists. Furthermore, in a few cases, an impalpable lesion is clearly seen on sonograms and yet poorly seen or not visible on mammograms. Accordingly, we studied the value of localizing impalpable masses with sonography in the operating room and of scanning excised specimens to confirm successful removal of the mass. All of the lesions were visible on preoperative sonograms. SUBJECTS AND METHODS: Twenty-six patients had sonographic examination of the breast in the operating room to guide the localization of an impalpable mass previously seen on sonograms. In eight patients, the lesion was poorly seen or not seen on conventional mammograms. Localizing techniques included one or more of the following: insertion of a needle, injection of dye, or simple marking on the skin. In 18 cases, sonography of the freshly excised specimen was done in the operating room. The sizes of the masses (13 fibroadenomas, 10 carcinomas, two cysts, and one tubular adenoma) measured on the sonograms ranged from 0.6 to 2.7 cm (mean +/- SD, 1.2 +/- 0.5 cm). RESULTS: In all 26 cases, the mass was clearly identified on sonograms obtained in the operating room. In all 18 cases in which it was used, sonography of the specimen correctly showed the presence or absence of the lesion. In two cases, sonographic determination of the absence of the lesion in the specimen prompted immediate reexcision, which was successful. CONCLUSION: Our experience shows that sonography in the operating room is a rapid and efficient method of localizing impalpable breast masses that have been seen on sonograms. Sonography of the specimen can indicate within seconds whether the excision has been successful. This technique is particularly valuable for masses that are not visible or only poorly visible on mammograms.

Breast↗

PubMed1994

Intraoperative lymphatic mapping for vulvar cancer.

OBJECTIVE: To determine the feasibility of intraoperative lymphatic mapping in patients with vulvar cancer. METHODS: Isosulfan blue was injected intradermally at the junction of tumor and normal skin in nine patients. We then attempted to identify the dye in the superficial lymphatic channels and in a superficial groin lymph node. RESULTS: The sentinel node was identified in seven of 12 groins in seven of the nine subjects studied. Six of the successful cases had unilateral lesions. The cases in which a sentinel node was not identified were both patients with midline lesions, including one whose scar was injected following a prior wide local excision of a perineal tumor and one who appeared to have direct drainage to the deep pelvic nodes. There were no technique-related complications. In no case was there a positive non-sentinel node in the presence of a negative sentinel node. CONCLUSION: Intraoperative lymphatic mapping is technically feasible in patients with vulvar cancer, particularly those with unilateral disease. Further experience is needed to evaluate the reliability of the technique in identification of groin node metastases.

Carcinoma, Squamous Cell↗

PubMed1994

Sarcoma of the breast: implications for extent of therapy. The M. D. Anderson experience.

BACKGROUND: Sarcoma of the breast is a rare clinical entity for which there are no prospective data about extent of surgery indicated or role of multimodality therapy. The purpose of this study was to examine one of the largest single institutional experiences to shed light on these clinical issues. METHODS: This study retrospectively reviewed 60 cases of sarcoma of the breast (cystosarcoma phyllodes excluded). RESULTS: For the entire series there was a median overall survival time (OS) of 67 months and a disease-free survival period (DFS) of 18 months. Tumors smaller than 5 cm were associated with a better DFS (p < 0.04) and OS (p < 0.009). Patients with tumors less than 5 cm in diameter did equally well whether treated by wide local excision or mastectomy. Angiosarcoma histologic characteristics were associated with longer OS than stromal sarcoma (p = 0.017), malignant fibrous histiocytoma (p = 0.075), or fibrosarcoma (p = 0.08). Axillary dissections did not recover any nodal metastasis; moreover, treatment in 75% of the patients with negative nodes subsequently failed. Regional lymph node metastases were always and only in the context of disseminated disease. Adjuvant chemotherapy and/or radiotherapy was associated with prolonged DFS (p = 0.015). There was a trend toward improved local control with adjuvant radiotherapy (p = 0.14). CONCLUSIONS: Lesions less than 5 cm should be treated by breast-preserving wide local excision, and adjuvant radiotherapy should be considered for selected subgroups. For tumors 5 cm or larger, a more aggressive approach seems appropriate; consideration should be given to neoadjuvant chemoradiation followed by margin-negative surgery (if possible). There is no demonstrable staging or therapeutic role for routine axillary dissection.

Adolescent↗

PubMed1993

Increase in the ability of human cancer cells to induce cytotoxic T lymphocytes by ultraviolet irradiation.

The roles of ultraviolet-B (UV) radiation in the immunogenicity of human cancer cells have not been fully studied. We have investigated the effects of UV radiation on metastatic melanoma and renal cell carcinoma cells with regard to MHC antigen expression and the ability to induce cytotoxic T lymphocyte (CTL) activity in peripheral blood mononuclear cells (PBMC) or tumor-infiltrating lymphocytes (TIL) against untreated autologous tumor cells. UV radiation respectively decreased or increased MHC class I expression of freshly isolated tumor cells or cultured tumor cells, and also decreased MHC class I expression of starved cultured tumor cells. It increased the ability of both freshly isolated and cultured tumor cells to induce CTL activity from PBMC against untreated autologous tumor cells. UV-irradiated subclones that were more susceptible to CTL lysis were more potent for CTL induction from TIL than either an untreated parental clone or a UV-irradiated subclone that was resistant to CTL lysis. In summary, UV radiation increased the ability of tumor cells to induce CTL activity without a corresponding effect on MHC antigen expression.

Carcinoma, Renal Cell↗

PubMed1993

Prognostic implications of DNA index in patients with stage III cutaneous melanoma.

DNA flow cytometry of the lymph node metastases from 56 patients was used to retrospectively evaluate the prognostic significance of DNA ploidy in patients with stage III melanoma. The findings were correlated with traditional prognostic factors and patient survival. Multivariate regression analysis revealed that, in addition to the number of positive lymph nodes and patient gender, the DNA index was a significant predictor of patient survival (all p < 0.03). Within this cohort of patients, the patients with the poorest prognoses were those with DNA indices greater than 2 (at least tetraploid), more than three positive lymph nodes, and male gender. There was a significant survival difference among the patients having zero, one, or two of these risk factors (p < 0.001). Our results indicate that DNA analysis of melanoma metastases by flow cytometry provides an additional discriminating factor for predicting patient outcome after therapeutic lymph node dissection. This information may be useful in directing patients with stage III melanoma at higher risk for recurrence into clinical trials of more aggressive systemic adjuvant therapy.

Adolescent↗

PubMed1993

Cytokine production and immune cell activation in melanoma patients treated with liposomal muramyl tripeptide (CGP 19835A lipid).

We conducted a pilot study using liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (L-MTP-PE) preoperatively in patients with stage III or IV resectable melanoma who were at high risk for recurrence. Patients received L-MTP-PE for 1 month before surgery and then 5 months postoperatively. Several immune parameters were monitored during preoperative therapy to search for correlations with clinical (tumor) response. The 18 patients were classified into three groups according to their responses and disease-free intervals: no evidence of disease (NED) at week 24 of therapy, relapse during therapy and progressive disease on therapy noted at the time of surgery. Six of nine patients in the NED group demonstrated increased monocyte tumoricidal activity (MTA) during week 1 of therapy. MTA increased in three of the six patients in the relapse group. MTA did not increase in the three patients who had progressive disease on therapy. Plasma neopterin levels were elevated by 72 h following the first L-MTP-PE dose in all 18 patients. Circulating levels of tumor necrosis factor were elevated in 15 of 16 patients tested, and IL-6 levels were elevated in all 18 patients. Melanoma cells from all three patients with progressive disease at the time of surgery proliferated well in vitro, whereas tumor cells from 10 of the 15 patients in the other two groups did not proliferate. There were no discernible differences among the three groups in the magnitude of IL-2-induced proliferation of tumor infiltrating lymphocytes. However, IL-2-activated TILs from the NED group exhibited cytotoxicity against autologous tumor cells in vitro. In summary, whereas L-MTP-PE stimulated several immunologic responses in all patients, the only two parameters that correlated with clinical status were MTA and the tumor proliferation assay. These two biologic assays could serve to distinguish potential responders from nonresponders early in the course of treatment.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1992

Distribution of autologous tumor-specific cytotoxic T lymphocytes in human metastatic melanoma.

The study of specific immunity in human cancers has been hampered by the elusive distribution and heterogeneity of effector cells. In this study, we have investigated the distribution of autologous melanoma-specific cytotoxic T lymphocytes (CTLs) in 18 different distant metastases from melanomas (9 non-visceral and 9 visceral metastases). Uncultured cells from tumors were provided directly for the establishment of T-cell clones using limiting dilution analysis to avoid any possible effects of in vitro sensitization of T cells to coexisting tumor cells. Autologous tumor specific CTL clones were detected in 6 of 18 tumors (33%, 4 non-visceral and 2 visceral metastases). The majority of CTL clones (35 of 46 and 17 of 19) in 2 patients with HLA class-I A2 haplotype failed to lyse either A2+ or A2- allogeneic melanoma cells, although anti-class-I (monomorphic) MAb inhibited their cytotoxicity. The remaining 11 of 46 and 2 of 19 CTL clones showed A2-restricted cytotoxicity. Autologous tumor-specific cytotoxicity was also detected after polyclonal culture of these tumor-infiltrating lymphocytes (TILs) in 8 of 16 tumors (50%, 5 non-visceral and 3 visceral metastases). These results suggest that tumor-specific T cells exist at tumor sites in at least one-third of distant metastases of melanomas and could be induced by the addition of IL-2 in at least half of the tumors. Tumor-specific T cells were detectable more often in non-visceral than in visceral metastases.

Antibodies, Monoclonal↗

PubMed1992

Oligoclonal expansion of V beta 8+ cells in interleukin-2-activated T cells residing in subcutaneous metastatic melanoma.

Oligoclonality was investigated in interleukin-2 (IL-2)-activated T cells (tumor-infiltrating lymphocytes, TILs) residing in metastatic melanomas using seven different monoclonal antibodies (mAbs) specific for T-cell receptor (TCR) V alpha or V beta regions and flow cytometry. IL-2-activated TILs from 25 of 42 metastatic melanomas (60%) displayed oligoclonal expansion, whereas IL-2-activated peripheral bllod mononuclear cells (PBMCs) from only 2 of 20 patients (10%) did so during 2-5 weeks in culture. Skin-derived lymphocytes from 20 patients were cultured; only four samples proliferated and none showed oligoclonal expansion. Preferential oligoclonal expansion of TILs was observed in V beta 8+ cells (10/42, P less than 0.05), V beta 6.7+ cells (7/42, P less than 0.05), and V alpha 2+ cells (7/42, not significant). Oligoclonal expansion of V beta 8+ cells was primarily found in T cells from subcutaneous metastases (8/20 cases, P less than 0.05), whereas that of V beta 6.7+ cells and V alpha 2+ cells was also found in T cells from lymph node or organ metastases. These mAbs to TCR V regions stimulated effector TILs to produce interferon-gamma, but not IL-2 or IL-4. Subcutaneous tumor-specific (V beta 8+ cells) and non-specific (V beta 6.7+ cells and V alpha 2+ cells) oligoclonalities were observed in IL-2-activated melanoma TILs, suggesting different immune responses among different sites of metastases.

Antibodies, Monoclonal↗

PubMed1992

Role of uncultured human melanoma cells in the proliferation of autologous tumor-specific cytotoxic T lymphocytes.

The role of uncultured melanoma cells in the proliferation of autologous tumor-specific cytotoxic T lymphocytes (CTLs) was investigated. Uncultured autologous tumor cells by themselves induced modest, but significant, proliferation in 10 of 13 (77%) CTL clones and in only two of nine non-CTL clones. Uncultured allogenic melanoma cells mostly failed to induce CTL proliferation. Autologous tumor-induced CTL proliferation declined with increasing age of the culture. It did not correlate with IL-2 receptor-alpha expression or was not inhibited by addition of anti-IL-2 antibody to the culture. It was inhibited by pretreatment of tumor cells with anti-MHC class II, but not -MHC class I mAb. IL-2 alone was sufficient for the potent proliferation of five of nine CTL clones. In all these five CTL clones, autologous tumor cells suppressed IL-2-induced proliferation. The remaining four CTL clones, however, required both uncultured autologous melanoma cells and IL-2 for the proliferation. IL-4 or IL-6, in particular IL-6, facilitated IL-2-induced CTL proliferation, but not their cytotoxicity. In summary, uncultured melanoma cells by themselves induced modest levels of CTL proliferation in the context of MHC class II antigens, whereas they suppressed IL-2-induced CTL proliferation in more than half of the clones.

Antibodies, Monoclonal↗