What's hot on the prostate?
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Journal Article↗
Biomedical subjects
A Belldegrun
Publications and source records attributed to A Belldegrun.
Immunomodulatory dendritic cells generated from nonfractionated bulk peripheral blood mononuclear cell cultures induce growth of cytotoxic T cells against renal cell carcinoma.
Dendritic cells (DCs) loaded with tumor antigens have the potential to become a powerful tool for clinical cancer treatment. Recently, the authors showed that a tumor-specific immune response can be elicited in culture via stimulation with autologous renal tumor lysate (Tuly)-loaded DCs that were generated from cytokine-cultured adherent peripheral blood mononuclear cells (PBMCs). Here, the authors show that immunomodulatory DCs can be generated directly from nonfractionated bulk PBMC cultures. Kinetic studies of DC differentiation and maturation in PBMC cultures were performed by monitoring the acquisition of DC-associated molecules using fluorescence-activated cell sorting analysis to determine the percentage of positive immunostained cells and the mean relative linear fluorescence intensity (MRLFI). Compared with conventional adherent CD14+ cultures, which have mostly natural killer, T, and B cells removed before cytokine culture, bulk PBMC cultures exhibited an early loss of CD14+ cells (day 0 = 78.8%, day 2 = 29.6% versus day 0 = 74%, day 2 = 75%) with an increase in yield of mature DCs (DC19- CD83+) (day 5 = 17%, day 6 = 21%, day 7 = 22% versus day 5 = 11%, day 6 = 15%, day 7 = 23%). Although a comparable percentage of DCs expressing CD86+ (B7-2), CD40+, and HLA-DR+ were detected in both cultures, higher expression levels were detected in DCs derived from bulk culture (CD86 = MRLFI 3665.1 versus 2662.1 on day 6; CD40 = MRLFI 1786 versus 681.2 on day 6; HLA-DR = MRLFI 6018.2 versus 3444.9 on day 2). Cytokines involved in DC maturation were determined by polymerase chain reaction demonstrating interleukin-6 (IL-6), IL-12, interferon-gamma, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor-alpha mRNA expression by bulk culture cells during the entire 9-day culture period. This same cytokine mRNA profile was not found in the conventional adherent DC culture. Autologous renal Tuly (30 micrograms protein/10(7) PBMCs) enhanced human leukocyte antigen expression by DCs (class I = 7367.6 versus 4085.4 MRFLI; class II = 8277.2 versus 6175.7 MRFLI) and upregulated cytokine mRNAs levels. Concurrently, CD3+ CD56-, CD3+ CD25+, and CD3+ TCR+ cell populations increased and cytotoxicity against autologous renal cell carcinoma tumor target was induced. Specific cytotoxicity was augmented when cultures were boosted continuously with IL-2 (20 U/mL biological response modifier program) plus Tuly stimulation. These results suggest that nonadherent PBMCs may participate in enhancing DC maturation. Besides the simplicity of this culture technique, bulk DC cultures potentially may be used with the same efficiency as conventional purified DCs. Furthermore, bulk culture-derived DCs may be used directly in vivo as a tumor vaccine, or for further ex vivo expansion of co-cultured cytotoxic T cells to be used for adoptive immunotherapy.
Antigen-Presenting Cells↗
Is adrenalectomy a necessary component of radical nephrectomy? UCLA experience with 511 radical nephrectomies.
PURPOSE: We determine the incidence and characteristics of adrenal involvement in localized and advanced renal cell carcinoma, and evaluate the role of adrenalectomy as part of radical nephrectomy. MATERIALS AND METHODS: The records of 511 patients undergoing radical nephrectomy with ipsilateral adrenalectomy for renal cell carcinoma at our medical center between 1986 and 1998 were reviewed. Mean patient age was 63.2 years (range 38 to 85), and 78% of the subjects were males and 22% were females. Patients were divided into subgroups of 164 with localized (stage T1-2 tumor, group 1) and 347 with advanced (stage T3-4N01M01, group 2) renal cell carcinoma. Staging of tumors was performed according to the 1997 TNM guidelines. A retrospective review of preoperative computerized tomography (CT) of the abdomen was performed. Radiographic findings were subsequently compared to postoperative histopathological findings to assess the predictive value of tumor characteristics and imaging in determining adrenal metastasis. RESULTS: Of the 511 patients 29 (5.7%) had adrenal involvement. Average size of the adrenal tumor was 3.86 cm. (standard deviation 1.89). Tumor stage correlated with probability of adrenal spread, with T4, T3 and T1-2 tumors accounting for 40%, 7.8% and 0.6% of cases, respectively. Upper pole intrarenal renal cell carcinoma most likely to spread was local extension to the adrenal glands, representing 58.6% of adrenal involvement. In contrast, multifocal, lower pole and mid region renal cell carcinoma tumors metastasized hematogenously, representing 32%, 7% and 4% of adrenal metastasis, respectively. The relationship between intrarenal tumor size (mean 8.9 cm., range 3 to 17) and adrenal involvement (independent of stage) was not statistically significant. Renal vein thrombus involvement was demonstrated in 8 of 12 cases (67%) with left and 2 of 9 (22%) with right adrenal involvement. Preoperative CT demonstrated 99.6% specificity, 99.4% negative predictive value, 89.6% sensitivity and 92.8% positive predictive value for adrenal involvement by renal cell carcinoma. CONCLUSIONS: With a low incidence of 0.6%, adrenal involvement is not likely in patients with localized, early stage renal cell carcinoma and adrenalectomy is unnecessary, particularly when CT is negative. In contrast, the 8.1% incidence of adrenal involvement with advanced renal cell carcinoma supports the need for adrenalectomy. Careful review of preoperative imaging is required to determine the need for adrenalectomy in patients at increased risk with high stage lesions, renal vein thrombus and upper pole or multifocal intrarenal tumors. With a negative predictive value of 99.4%, negative CT should decrease the need for adrenalectomy. In contrast, positive findings are less reliable given the relatively lower positive predictive value of this imaging modality. Although such positive findings may raise suspicion of adrenal involvement, they may not necessarily indicate adrenalectomy given the low incidence, unless renal cell carcinoma with risk factors, such as high stage, upper pole location, multifocality and renal vein thrombus, is present.
Adrenal Gland Neoplasms↗
Expanding the indications for surgery and adjuvant interleukin-2-based immunotherapy in patients with advanced renal cell carcinoma.
PURPOSE: To determine the role of surgery and adjuvant interleukin (IL)-2-based immunotherapy in the treatment of patients with advanced metastatic renal cell carcinoma PATIENTS AND METHODS: The survival of 354 consecutive patients with metastatic renal cell carcinoma treated with IL-2-based immunotherapy through the UCLA Medical Center Kidney Cancer Program was analyzed There were five groups of patients. Patients who initially presented with metastatic disease received either (1) IL-2 therapy with primary tumor in place; (2) nephrectomy followed by IL-2 therapy, or (3) nephrectomy followed by immunotherapy with IL-2 plus tumor-infiltrating lymphocytes. Patients who underwent nephrectomy for localized disease were divided into two groups: (4) those who developed metastatic disease > or = 6 months after nephrectomy and then received IL-2 therapy; and (5) those who developed metastatic disease < 6 months after nephrectomy and then received IL-2 therapy. Kaplan-Meier survival curves were generated for all patient groups. RESULTS: Among patients who received IL-2-based immunotherapy with their primary tumor in place (group 1; n = 36), 1- and 2-year survival rates were 29% and 4%, respectively, compared with 1- and 2-year survival rates of 67% and 44%, respectively, for all similar patients who underwent nephrectomy prior to IL-2 therapy (n = 235). Among patients initially presenting with metastatic disease who underwent nephrectomy followed by IL-2 therapy without tumor-infiltrating lymphocytes (group 2; n = 69), the 1- and 2-year survival rates were 53% and 25%, respectively. The best survival was observed in patients treated with nephrectomy followed by IL-2 plus tumor-infiltrating lymphocyte therapy (group 3; n = 102), which yielded 1- and 2-year survival rates of 73% and 55%, respectively. Among patients initially undergoing nephrectomy for localized disease, patients receiving IL-2-based therapy for subsequent metastasis > or = 6 months following nephrectomy (group 4; n = 128) had 1- and 2-year survival rates of 64% and 40%, respectively, compared with 45% and 15%, respectively, for patients developing metastasis < 6 months after nephrectomy (group 5; n = 19). CONCLUSION: The role of surgery prior to IL-2-based immunotherapy remains controversial Our data demonstrate that aggressive surgery is safe, causing minimal morbidity despite extensive tumor involvement, and significantly improves survival outcomes in patients with metastatic renal cell carcinoma when carried out in conjunction with an IL2-based immunotherapy regimen.
Carcinoma, Renal Cell↗
Adoptive cellular therapy.
We provide a current review of adoptive cellular therapy in the management of metastatic renal cell carcinoma. A comprehensive literature review of peer-reviewed articles on the development and use of adoptive cellular immunotherapy was performed. Renal cell carcinoma is a highly immunogenic tumor that has proven resistant to standard cytotoxic chemotherapy, but has shown reproducible response to immune-based therapy. In an effort to improve responses, a variety of adoptive cellular strategies have been devised and tested in the setting of metastatic disease. Among the techniques developed, the use of lymphokine-activated killer (LAK) cells, autolymphocyte therapy (ALT), and tumor-infiltrating lymphocytes (TIL) have been the best studied. While further trials are ongoing, thus far, these approaches have not consistently shown benefit in comparison to standard immune-based treatment with biologic response modifiers, most importantly, high-dose bolus interleukin-2 (IL-2). Future approaches, including the use of dendritic cells (DC) to facilitate the development of tumor vaccines, are encouraging. Advanced renal cell carcinoma continues to inspire research of promising new cellular immunotherapeutics. The experience with LAK, ALT, and TIL has greatly increased our understanding of tumor immunobiology, and has led to the ongoing development of new technology, including DC, vaccine, and antibody therapy.
Adjuvants, Immunologic↗
Gene and immune-based therapies for genitourinary malignancies: current status and future prospects.
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Carcinoma, Renal Cell↗
Blood loss and the need for transfusion in patients who undergo partial or radical nephrectomy for renal cell carcinoma.
PURPOSE: We assessed blood loss and subsequent transfusion associated with nephrectomy performed for suspected renal cell carcinoma to establish guidelines for preoperative autologous blood donation and identify a subgroup of patients that may benefit from erythropoietin administration. MATERIALS AND METHODS: We retrospectively reviewed the charts of 211 patients who underwent partial (73%) or radical (23%) nephrectomy for presumed renal cell carcinoma at our institution between 1990 and 1999. Patients were divided into groups 1-44.5% treated with radical nephrectomy for localized disease, 2-21.3% radical nephrectomy for metastatic lesions invading the renal vasculature or inferior vena cava, 3-8% radical nephrectomy for metastatic disease with locally extensive lesions and 4-26.5% partial nephrectomy for localized lesions. Patient charts were evaluated for preoperative and postoperative hematocrit, estimated blood loss, transfusions received, surgical complications and underlying disease. RESULTS: Median estimated blood loss was 200, 400, 250 and 555 cc in groups 1 to 4, respectively. However, patients in groups 2 and 3 had a substantially greater range of blood loss than those in groups 1 and 4, respectively. The incidence of those with a blood loss of greater than 1 l. was 7%, 36%, 24% and 11% in groups 1, to 4, respectively. The incidence of those requiring transfusion was significantly lower in group 1 than in groups 2 to 4 (18% versus 44%, 24% and 30%, respectively, p <0.009). Mean transfusion requirement plus or minus standard deviation was significantly greater in groups 2 and 3 than in 1 and 4 (2.3 +/- 1.08, 5.5 +/- 4.4, 11.3 +/- 9.6 and 2.3 +/- 1.7 units, respectively, p <0.05). No significant difference was noted in the change in hematocrit as a result of surgery in the 4 groups (p >0.05). Similarly underlying disease and operative complications did not have a significant effect on blood loss or transfusion (p >0. 05). CONCLUSIONS: Radical or partial nephrectomy for localized renal cell carcinoma leads to consistent and well tolerated operative blood loss that rarely results in the need for substantial transfusion. In contrast, nephrectomy for advanced disease may cause a risk of greater blood loss and subsequent need for the transfusion of multiple units of blood. While preoperative autologous blood donation may have limited value in this regard due to the high cost and number of units needed, preoperative erythropoietin administration may be a viable option. Prospective randomized studies are currently planned.
Adolescent↗
Therapeutic strategies, predicting outcomes in patients with renal cell and transitional cell carcinomas.
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Journal Article↗
Immunotherapy and peripheral-blood transplant for metastatic renal cell carcinoma.
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Journal Article↗
Immune and genetic therapies for advanced renal cell carcinoma.
Although we have witnessed advances in many aspects of cancer research and therapy in recent years, the ability to cure the majority of patients with advanced renal cell carcinoma (RCC) remains elusive. At the same time, it has become increasingly apparent that a better understanding of the genetic alterations and immune dysregulations in RCC will play a key role in finding a treatment. Therefore, clinical trials directed at specific genetic alterations and studies exploiting components of the immune system are being conducted. These studies provide new hope for an improved outlook for patients presenting with advanced RCC. The future prospects of RCC therapy will be, without doubt, built on the foundation of current investigative efforts in gene and immune therapy. This article reviews the current role of immunotherapy and gene therapy in the management of metastatic RCC. Finally, current clinical trials focusing on gene and immune therapies are listed.
Journal Article↗
Evidence for clonal outgrowth of androgen-independent prostate cancer cells from androgen-dependent tumors through a two-step process.
Prostate cancers require androgen for growth but progress to an androgen-independent stage under the selective pressure of androgen ablation therapy. Here we describe a novel human prostate cancer xenograft (LAPC-9) propagated by serial passage in male severe combined immunodeficient mice that expresses prostate-specific antigen and wild-type androgen receptor. In response to castration, LAPC-9 cells undergo growth arrest and persist in a dormant, androgen-responsive state for at least 6 months. After prolonged periods of androgen deprivation, spontaneous androgen-independent outgrowths develop. Thus, prostate cancers progress to androgen independence through two distinct stages, initially escaping dependence on androgen for survival and, subsequently, for growth. Through the use of serial dilution and fluctuation analysis, we provide evidence that the latter stage of androgen independence results from clonal expansion of androgen-independent cells that are present at a frequency of about 1 per 10(5)-10(6) androgen-dependent cells. We conclude that prostate cancers contain heterogeneous mixtures of cells that vary in their dependence on androgen for growth and survival and that treatment with antiandrogen therapy provides selective pressure and alters the relative frequency of these cells, thereby leading to outgrowths of androgen-independent cancers.
Androgens↗
Sensitization of immunoresistant prostate carcinoma cell lines to Fas/Fas ligand-mediated killing by cytotoxic lymphocytes: independence of de novo protein synthesis.
BACKGROUND: We recently reported that drug-resistant prostate tumor cells (DU145, PC-3) are resistant to Fas-mediated killing by cytotoxic lymphocytes, and that this resistance can be overcome by treatment with subtoxic concentrations of chemotherapeutic drugs. Fas belongs to the tumor necrosis factor (TNF) family of receptors. Since resistance to TNF-alpha-mediated killing has been shown to be due, in part, to the presence of protective factors and that inhibitors of protein synthesis can sensitize cells to TNF-alpha killing, we hypothesized that resistance to Fas-mediated killing may be due to similar mechanisms. Since sensitization is achieved with chemotherapeutic drugs, and some chemotherapeutic drugs can also inhibit protein synthesis, we tested whether sensitization of prostate tumor cells to Fas ligand (Fas-L) occurred through inhibition of protein synthesis in a manner analogous to that of TNF-alpha. METHODS: The effect of chemotherapeutic drugs on protein synthesis in DU145 and PC-3 cells was characterized by (3)H-leucine incorporation assays. We also determined the ability of inhibitors of protein synthesis and chemotherapeutic drugs to sensitize Fas and TNF-resistant DU145 cells to killing. The ability of RNA (actinomycin-D, Act-D) and protein synthesis inhibitors (cyclohexamide (CHX), emetine) to block drug-mediated sensitization to Fas-L killing was analyzed. Sensitivity to Fas-L killing was determined by the (51)Cr-release assay using human lymphokine-activated killer cells (LAK) and tumor-infiltrating lymphocyte (TIL) effector cells and the murine Fas-L-expressing PMMI cells. RESULTS: The drugs cis-diamminedichloroplatinum (II) (CDDP), adriamycin (ADR), and etoposide (VP-16) sensitized DU145 and PC-3 cells to Fas killing. CDDP and ADR, which sensitized DU145 and PC-3 cells to Fas-L- and TNF-mediated killing, inhibited de novo protein synthesis in both cell lines, while VP-16 only inhibited protein synthesis in DU145 cells. Further, neither CHX nor emetine sensitized DU145 or PC-3 cells to Fas-L-mediated killing, despite blocking >90% de novo protein synthesis. In contrast, CDDP, VP-16, and the protein synthesis inhibitors, Act-D and CHX sensitized DU145 cells to TNF-alpha killing. Finally, pretreating cells with protein synthesis inhibitors (CHX, emetine) did not abrogate drug-mediated sensitization to Fas-mediated killing. CONCLUSIONS: These findings demonstrate that downregulation of protective factors by protein synthesis inhibition may not be the primary mechanism of drug-mediated sensitization to Fas-L killing in prostate cell lines. These findings also suggest that drug-mediated sensitization to Fas-L killing may be due to modifications of preexisting gene products that participate in Fas-L-mediated apoptosis.
Animals↗
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) for treatment of prostate cancer: first results and review of the literature.
We present the involvement and association of TNF-related apoptosis-inducing ligand (TRAIL) with apoptosis. Its potential application as a therapeutic agent in urologic oncology is discussed. We have examined the sensitivity of prostate carcinoma cell lines DU145, PC3 and LNCaP to TRAIL-induced apoptosis and the expression of TRAIL receptors. Furthermore we looked into the sensitization of those prostate carcinoma cell lines to TRAIL-mediated apoptosis by low toxic levels of actinomycin-D. Furthermore, we review and discuss the pertinent literature on the molecular biology of TRAIL, its receptors and future potential for therapy in urologic oncology. Recent discovery and characterization of TRAIL has led to further broadening and insights into the apoptotic process. Based on preceding in-vitro studies, the first in-vivo study using TRAIL has been conducted and published in 1999. Systemic application of TRAIL in severe combined immune deficient (SCID) mice resulted in tumor regression of subcutaneous implanted mammary and colon cancer and several groups are looking into TRAIL sensitivity of prostate cancer and renal cancer cellines. Our in-vitro data revealed a significant increase of apoptotic cell death rate following the combined application of TRAIL with actinomycin-D. Our results suggest that the combination of TRAIL and ActD may be a therapeutic option in the treatment of drug/hormone refractory prostate carcinoma. In the future TRAIL may be used in combination therapy with other immunotherapies or gene therapies providing a synergistic effect or enhancing the efficacy of chemotherapeutic or radiotherapeutic regimens.
Journal Article↗
What's hot in the prostate? Prostate Cancer screening approved in the USA and Highlights from the Annual Meeting of The Western Section American Urological Association.
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Journal Article↗
Metastatic renal cell carcinoma with concurrent inferior vena caval invasion: long-term survival after combination therapy with radical nephrectomy, vena caval thrombectomy and postoperative immunotherapy.
PURPOSE: We report our experience using aggressive multimodal therapy in a high risk group of patients with metastatic renal cell carcinoma and concurrent inferior vena caval extension. MATERIALS AND METHODS: We retrospectively reviewed the records of all patients in our kidney cancer database who had metastatic renal cell carcinoma and tumor thrombus extension into the inferior vena cava at the initial diagnosis. Patients were included in the study if they underwent radical nephrectomy and inferior venal caval thombectomy, and immunotherapy was planned for the postoperative period. Tumor size and grade, metastatic sites, level of vena caval extension, surgical complications and overall survival were obtained from the medical records. The primary end point analyzed was overall survival. RESULTS: We identified 31 cases of metastatic renal cell cancer with extensive disease and vena caval extension. Of the patients 23% had an isolated lung metastasis, and 53% had metastasis in the lung and at other sites. The remaining patients had involvement primarily at nonpulmonary metastatic sites, including lymph node in 38%, soft tissue in 13%, liver in 29% and bone in 10%. Average blood loss during nephrectomy was 3,200 cc (median 2,100) and the rate of major complications was 12%. Of the patients 80% underwent the full course of surgery and postoperative immunotherapy. At a mean followup of 18 months (34 for survivors) 26% of the patients are alive. Actuarial overall 5-year survival of the group was 17%. Tumor thrombus level did not correlate with overall survival, while immunotherapy, tumor grade and metastatic site provided significant prognostic information. In patients with an isolated pulmonary metastasis the 5-year survival rate was 43%, while in those with low grade tumors it was 52%. CONCLUSIONS: In contrast to the poor results of surgery only in patients with renal cell carcinoma and concurrent inferior venal caval invasion, reasonable 5-year survival may be achieved after combined aggressive surgery and immunotherapy. Patients in whom metastasis was limited to the lungs and those with grade 1 to 2 tumors had a better prognosis. With careful planning and experienced immunotherapists therapy may be completed in the majority of this high risk group of patients.
Adult↗
Sarcomatoid renal cell carcinoma: biologic behavior, prognosis, and response to combined surgical resection and immunotherapy.
PURPOSE: Sarcomatoid variants of renal cell carcinoma (RCC) are aggressive tumors that respond poorly to immunotherapy. We report the outcomes of 31 patients with sarcomatoid RCC treated with a combination of surgical resection and immunotherapy. PATIENTS AND METHODS: Patients were identified from the database of the University of California Los Angeles Kidney Cancer Program. We retrospectively reviewed the cases of 31 consecutive patients in whom sarcomatoid RCC was diagnosed between 1990 and 1997. Clinical stage, sites of metastasis, pathologic stage, and type of immunotherapy were abstracted from the medical records. The primary end point analyzed was overall survival, and a multivariate analysis was performed to distinguish any factors conferring an improved survivorship. RESULTS: Twenty-six percent of patients were male and 74% were female, and the median age was 59 years (range, 34 to 73 years). Length of follow-up ranged from 2 to 77 months (mean, 21.4 months). Twenty-eight patients (84%) had known metastases at the time of radical nephrectomy (67% had lung metastases and 40% had bone, 21% had liver, 33% had lymphatic, and 15% had brain metastases). Twenty-five patients (81%) received immunotherapy, including low-dose interleukin (IL)-2-based therapy (five patients), tumor-infiltrating lymphocyte-based therapy plus IL-2 (nine patients), high-dose IL-2-based therapy (nine patients), dendritic cell vaccine-based therapy (one patient), and interferon alpha-based therapy alone (one patient). Two patients (6%) achieved complete responses (median duration, 46+ months) and five patients (15%) achieved partial responses (median duration, 36 months). One- and 2-year overall survival rates were 48% and 37%, respectively. Using a multivariate analysis, age, sex, and percentage of sarcomatoid tumor (< or >50%) did not significantly correlate with survival. Improved survival was found in patients receiving high-dose IL-2 therapy compared with patients treated with surgery alone or any other form of immunotherapy (P = .025). Adjusting for age, sex, and percentage of sarcomatoid tumor, the relative risk of death was 10.4 times higher in patients not receiving high-dose IL-2 therapy. Final pathologic T stage did not correlate significantly with outcome, but node-positive patients had a higher death rate per year of follow-up than did the rest of the population (1.26 v 0.76, Cox regression analysis). CONCLUSION: Surgical resection and high-dose IL-2-based immunotherapy may play a role in the treatment of sarcomatoid RCCs in select patients.
Adult↗
Efficacy of nephron-sparing surgery for renal cell carcinoma: analysis based on the new 1997 tumor-node-metastasis staging system.
PURPOSE: To analyze the experience with nephron-sparing surgery as a treatment modality for renal cell carcinoma (RCC). PATIENTS AND METHODS: Between 1980 and 1997, 146 patients underwent partial nephrectomy at the University of California-Los Angeles Medical Center. A matched group of 125 patients who underwent radical nephrectomy at the same institution between 1986 and 1997 were selected for comparison. Patients were monitored for an average period of 57 months. Patients were staged according to both the 1997 and 1987 tumor-node-metastasis (TNM) staging criteria. Survival data were calculated in terms of both staging criteria. RESULTS: When comparing cancer-specific survival rates for patients with T1 lesions under both the 1987 and 1997 TNM staging criteria, no statistically significant difference in survival was noted (P =.53), although most of the tumors in our series measured < or = 4 cm. Patients with T2 lesions (1997 TNM) demonstrated a significant decrease in survival (66%) when compared with patients with T1 lesions (100%; P <.001). No statistically significant difference in survival for patients with T1 RCC treated with either radical or partial nephrectomy was noted (P =.219). Survival rates of partial and radical nephrectomies for patients with unilateral T1 RCC and a normal contralateral kidney also were not significantly different (P =.53). In contrast, for patients with lesions greater than T1, survival rates were significantly higher with radical versus partial nephrectomy (P =.001). CONCLUSION: Partial nephrectomy has become an effective method of treating T1 RCC lesions as categorized by both the 1987 and the revised 1997 TNM staging criteria. Selected patients with localized unilateral RCC lesions less than 7 cm (ideally, < 4 cm) and a normal contralateral kidney will benefit from partial nephrectomy.
Adult↗
Presentation of renal tumor antigens by human dendritic cells activates tumor-infiltrating lymphocytes against autologous tumor: implications for live kidney cancer vaccines.
The clinical impact of dendritic cells (DCs) in the treatment of human cancer depends on their unique role as the most potent antigen-presenting cells that are capable of priming an antitumor T-cell response. Here, we demonstrate that functional DCs can be generated from peripheral blood of patients with metastatic renal cell carcinoma (RCC) by culture of monocytes/macrophages (CD14+) in autologous serum containing medium (RPMI) in the presence of granulocyte macrophage colony-stimulating factor and interleukin (IL) 4. For testing the capability of RCC-antigen uptake and processing, we loaded these DCs with autologous tumor lysate (TuLy) using liposomes, after which cytometric analysis of the DCs revealed a markedly increased expression of HLA class I antigen and a persistent high expression of class II. The immunogenicity of DC-TuLy was further tested in cultures of renal tumor infiltrating lymphocytes (TILs) cultured in low-dose IL-2 (20 Biologic Response Modifier Program units/ml). A synergistic effect of DC-TuLy and IL-2 in stimulating a T cell-dependent immune response was demonstrated by: (a) the increase of growth expansion of TILs (9.4-14.3-fold; day 21); (b) the up-regulation of the CD3+ CD56- TcR+ (both CD4+ and CD8+) cell population; (c) the augmentation of T cell-restricted autologous tumor lysis; and (d) the enhancement of IFN-gamma, tumor necrosis factor-alpha, granulocyte macrophage colony-stimulating factor, and IL-6 mRNA expression by TILs. Taken together, these data implicate that DC-TuLy can activate immunosuppressed TIL via an induction of enhanced antitumor CTL responses associated with production of Thl cells. This indicates a potential role of DC-TuLy vaccines for induction of active immunity in patients with advanced RCC.
Antigen Presentation↗