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PubMed1996

IL-15 can substitute for the marrow microenvironment in the differentiation of natural killer cells.

NK cells require an intact bone marrow microenvironment to acquire lytic function. In mice rendered osteopetrotic by 17beta-estradiol treatment, NK1.1 positive cells are arrested in a nonlytic state. Culture with as little as 2 ng/ml of murine IL-15 (mIL-15), a cytokine produced by macrophages and stromal cells, causes these immature NK1.1+ cells to acquire lytic activity. By contrast, approximately 10- to 50-fold greater amount of mIL-2 was required to induce similar level of cytotoxicity. After culture with mIL-15, the relatively low expression of B220, CD11b, and Ly-49 molecules on immature NK1.1+ cells was increased to levels comparable to those of mature splenic NK1.1+ cells. mIL-15 also caused a greater expansion of NK1.1+CD3- cells as compared with NK1.1+CD3+ cells. We conclude that IL-15 is a specific maturation factor for NK cells and that it can mimic the marrow microenvironment in vitro.

Animals↗

PubMed1996

Genetic instability induced by the tumor microenvironment.

The tumor microenvironment is characterized by regions of fluctuating hypoxia, low pH, and nutrient deprivation. To determine the genetic consequences of growth under these conditions, we used a tumorigenic cell line carrying a recoverable, chromosomally based lambda phage shuttle vector designed to report mutations without the need for genetic selection of mutant cells. The cells were grown in parallel either in culture or as tumors in nude mice. The frequency of mutations arising in cells within the tumors was found to be 5-fold higher than that in otherwise identical cells grown in culture. A distinct pattern of mutation was also seen, with significantly more deletions and transversions in the tumors than in the cell cultures. Furthermore, exposure of the cultured cells to hypoxia produced an elevated mutation frequency and a mutation pattern similar to that seen in the tumors. These results indicate that the conditions within solid tumors are mutagenic and suggest that a fundamental mechanism of tumor progression in vivo is genetic instability induced by the tumor microenvironment.

Animals↗

PubMed1997

Early transplantation to a normal microenvironment prevents the development of Steel hematopoietic stem cell defects.

Our previous results showed that hematopoietic stem cells from 16-week-old Sl/Sl(d) mice are not as competitive as congenic +/+ control stem cells. Possible explanations for these findings are that the Steel stem cells are either inherently defective or lose competitive ability by residence in an environment lacking membrane-bound Steel factor. In the present report, any long-term effects of the Steel microenvironment were eradicated by transferring neonatal Sl(d)/Sl(d) marrow and spleen cells into an irradiated but otherwise normal adult hematopoietic microenvironment. Host cells were completely replaced by donor cells within 6 weeks. Eight months after transplantation, the Sl(d)/Sl(d) and similarly treated +/+ littermate control cells from the primary recipient marrow were competed against genetically marked normal cells in an irradiated secondary host. The Steel cells were as competitive as the control cells demonstrating that Steel stem cells are not inherently defective. Results suggest that the stem cells, when retained in the mutant environs into adulthood, are either reduced in number or phenotypically altered by lack of the membrane-bound Steel factor.

Animals↗

PubMed1998

Identification of distinct elements of the stromal microenvironment that control human hematopoietic stem/progenitor cell growth and differentiation.

Using a novel collection of conditionally immortalized mouse stromal cell clones, we evaluated the role of distinct elements of the hematopoietic microenvironment in supporting and regulating the growth, division, and differentiation of a candidate human stem cell population (CD34+/CD38-). We found functional diversity in the capacity of different stromal cell clones to support the growth of primitive (CD34+/CD38-) and committed (CD34+/CD38+) hematopoietic progenitors and their differentiation into mature hematopoietic cells (CD34-/CD45+). Among the stromal cell clones that supported long-term hematopoiesis, we identified two clones that induced expansion of CD34+ progenitor/stem cells during the first 4 weeks of coculture and that supported the maintenance of this CD34+ population for up to 10 weeks in vitro. However, these two clones appeared to represent two different microenvironments with regard to the signals they provide to the different CD34+ progenitor subpopulations: One stromal clone preserved a pool of undifferentiated, relatively quiescent (CD34+/CD38-) progenitor cells, allowing their differentiation at a low rate into more committed (CD34+/CD38+) progenitors; the other fostered a more extensive and rapid differentiation of all CD34+/CD38- progenitors into CD34+/CD38+ cells, preferentially maintaining this committed population at a higher rate of cell division. These stromal cell clones were also able to support the proliferation and differentiation of CD34+/CD38- cells in conditions in which progenitor-stroma contact was prevented. This collection of stromal cell clones may represent a unique tool for the study of stromal regulators of hematopoiesis as well as for the support of gene transfer into hematopoietic progenitor cells.

Animals↗

PubMed1998

Microlithiasis in parotid sialadenosis and chronic submandibular sialadenitis is related to the microenvironment: an ultrastructural and microanalytical investigation.

AIMS: Microlithiasis was investigated in parotid sialadenosis and chronic submandibular sialadenitis to determine if it relates to the glandular microenvironment as has been found experimentally. METHODS AND RESULTS: Semithin sections were stained by a mixture of methylene blue and Azure II followed by basic fuchsin, which stains calcified parts of microliths red and organic parts green, and ultrathin sections were examined electron microscopically and microanalytically. Microliths in sialadenosis were found in periacinar stroma, in which necrotic acinar cells were found, and in parenchyma, and consisted of consolidated organic material with little or no crystalline calcium. Microliths in sialadenitis were found in stroma, particularly around intercalary ducts, in lumina and in parenchyma, and contained much crystalline calcium. Macrophages enclosed some microliths. CONCLUSIONS: The paucity of calcium in microliths in sialadenosis and the abundance in sialadenitis relates to the glandular calcium. The periacinar distribution of microliths in sialadenosis possibly relates to formation in periacinar necrotic debris. The distribution of microliths in sialadenitis around intercalary ducts possibly relates to formation in matrix vesicles formed from atrophic parenchyma, and in lumina to formation in stagnant secretory material. Microliths appear to be scavenged by macrophages. Thus the experimental finding that salivary microlithiasis relates to the microenvironment pertaining in humans.

Calcinosis↗

PubMed2026

Integrated Genomic and Tumor Microenvironment Subtyping Improved Risk Stratification in Primary Central Nervous System Lymphoma.

Current prognostic models fail to capture the biological complexity of primary central nervous system lymphoma (PCNSL). We integrated whole-genome sequencing and multiplex immunofluorescence in 68 treatment-naïve patients to define four genomic subtypes (C1, C2, C3, and C4) with divergent survival (C4 worst: median overall survival [OS], 26 months). In parallel, a novel tumor microenvironment (TME) classification based on CD8+T/M2 macrophage ratio stratified patients into High (> 1.5), Intermediate (0.8-1.5), and Low (< 0.8) groups. Unexpectedly, the Intermediate TME group showed the poorest outcomes (5-year OS: 10%). Integration revealed a lethal subgroup (C4 + Intermediate TME; 9.8% of cohort) with a median OS of 3.0 months (hazard ratio = 7.24, p = 0.006). Prognostic nomograms incorporating these subtypes showed promising discriminative performance in internal validation (C-index > 0.78), but external validation is needed. Together, these findings identify a high-risk biological subset and provide a hypothesis-generating framework for future biomarker-driven risk stratification and therapeutic discovery in PCNSL.

Humans↗

PubMed2027

Systematic Analysis of Tumor Microenvironment Using IOBR.

The Immuno-Oncology Biological Research (IOBR) package is an R-based analysis tool for exploring the tumor microenvironment (TME) and its influence on anti-tumor immunity. Built for high-throughput data-spanning both transcriptomic and genomic profiles-IOBR integrates six analytical modules, including transcriptomic data preprocessing, TME profiling, TME pattern identification, ligand-receptor interaction analysis, genome-TME interaction assessment, and visualization. In this chapter, we walk through a multi-omics workflow using example datasets, illustrating data preparation, distribution analyses, result interpretation, and graphical output. IOBR is open source and is available at https://github.com/IOBR/IOBR and a detailed GitBook ( https://iobr.github.io/book/ ) offers a complete manual and analysis guide for each function.

Tumor Microenvironment↗

PubMed2026

Metabolic convergence of diabetes and prostate cancer: from dysglycemia to tumor microenvironment reprogramming.

The relationship between diabetes mellitus and prostate cancer (PC) represents one of the most intriguing paradoxes in cancer epidemiology, with diabetic individuals exhibiting a reduced incidence of PC yet poorer prognosis following diagnosis. This apparent contradiction underscores the need for an integrated understanding of how systemic metabolic dysfunction influences prostate carcinogenesis and disease progression. The present review critically synthesizes contemporary epidemiological, mechanistic, and translational evidence to establish metabolic convergence as a unifying framework linking diabetes-associated metabolic abnormalities with PC biology. Current evidence indicates that chronic dysglycemia, hyperinsulinemia, insulin resistance, and endocrine perturbations orchestrate interconnected intracellular signaling networks involving PI3K-AKT-mTOR, AMPK, AGE-RAGE signaling, oxidative stress, mitochondrial dysfunction, and epigenetic reprogramming, collectively driving metabolic adaptation and tumor evolution. Beyond tumor-intrinsic mechanisms, diabetes profoundly remodels the prostate tumor microenvironment through alterations in stromal metabolism, cancer-associated fibroblast activation, adipocyte-tumor crosstalk, extracellular matrix (ECM) remodeling, hypoxic adaptation, and vascular dysfunction, while simultaneously promoting immunometabolic reprogramming characterized by macrophage polarization, T-cell dysfunction, immune checkpoint activation, and immune evasion. The review further examines the bidirectional interactions between antidiabetic therapies and PC treatment, critically evaluating the translational potential of metformin and emerging glucose-lowering agents within the context of precision metabolic therapeutics. Finally, future directions encompassing biomarker-guided patient stratification, longitudinal metabolic profiling, multi-omics integration, artificial intelligence, and clinically relevant mechanistic validation are discussed as essential components of next-generation precision oncology. Collectively, this review reframes diabetes as an active metabolic determinant of PC rather than a coincidental comorbidity and highlights metabolism-centered precision strategies as promising avenues for improving risk stratification, therapeutic decision-making, and clinical outcomes in diabetes-associated PC.

Humans↗

PubMed2026

Beyond oncogenesis: The emerging role of EZH2 in tumor microenvironment.

Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase and the catalytic component of Polycomb Repressive Complex 2, facilitates epigenetic modifications via the repressive H3K27me3 mark, consequently modulating the expression of numerous genes implicated in cellular proliferation and survival. Overexpression or dysregulation of EZH2 has been observed extensively across several malignancies, where it plays a major role in shaping the tumor microenvironment, promoting angiogenesis, cytokine secretion, and matrix remodeling. EZH2 mediates immune evasion, particularly in response to immunotherapy and checkpoint blockade. These interactions also position EZH2 as a key mediator of therapy resistance to chemotherapy, immunotherapy, and targeted therapy. Consequently, a comprehensive understanding of EZH2's function and its interactions within the TME and during cancer progression is crucial. This review aims to enhance the current understanding of EZH2 and its roles in the TME, cancer development, and therapeutic responses. This review will discuss the canonical and non-canonical functions of EZH2, summarize its established and evolving roles in cancer and the TME, and highlight its effects on tumor immunity and therapeutic efficacy.

Humans↗

PubMed2025

DNA damage repair gene alterations influence the tumor immune microenvironment in advanced non-small cell lung cancer.

PURPOSE: DNA damage response and repair (DDR) gene alterations contribute to genomic instability and increased tumor immunogenicity, yet their clinical significance in non-small cell lung cancer (NSCLC) remains unclear. Using a large real-world dataset, we evaluated the prevalence of DDR alterations and their relation to the tumor immune microenvironment in metastatic NSCLC. EXPERIMENTAL DESIGN: We retrospectively analyzed real-world data from patients with metastatic NSCLC using the Tempus AI database. Tumors were sequenced with Tempus xT DNA and xR RNA assays and classified based on the presence (DDRmt) or absence (DDRwt) of a pathogenic somatic alteration or copy number deletion in a DDR pathway gene. Associations between DDR alterations and immune cell infiltration, PD-L1 immunohistochemistry, tumor mutational burden (TMB), and microsatellite instability (MSI-H) were examined. RESULTS: Among 14,127 patients (median age = 67, 49% female), 5,276 (37%) were DDRmt. There was a higher prevalence of current/former smokers in the DDRmt group (86% vs. 82%; p<0.001). DDRmt tumors were more likely to have higher levels of TMB (median: 5.4 vs. 4.6; p<0.001), MSI-H (1.1 % vs. <0.1 %; p<0.001), and infiltrating CD8+ T cells (p=0.003) compared to DDRwt tumors. A lower frequency of macrophages (p<0.001) were observed among DDRmt compared with DDRwt tumors with no difference in PDL1 positivity. CONCLUSIONS: Among patients with metastatic NSCLC, 37% present with DDRmt tumors characterized by higher TMB, frequency of MSI-H, and changes in immune cell infiltrates. These findings provide insight into the immunogenic landscape of DDR-altered NSCLC and may inform biomarker selection and therapeutic strategies.

Humans↗

PubMed2026

Distinct spatial immune microenvironment features of different EGFR mutation subtypes in early-stage lung adenocarcinoma.

Epidermal growth factor receptor (EGFR) mutations are common in lung adenocarcinoma (LUAD), yet their influence on the spatial tumor immune microenvironment (TIME) in early-stage disease remains unclear. We characterized the spatial TIME in 144 treatment-naïve, early-stage LUADs using integrated genomic sequencing and multiplex immunohistochemistry (mIHC). Although EGFR-mutant tumors overall displayed reduced CD8 + T-cell infiltration compared with EGFR-wild-type tumors, substantial heterogeneity was observed among EGFR subtypes. Specifically, L858R and rare-variant subtypes exhibited higher tumor mutational burden, greater CD8 + T-cell density, and enrichment of T-cell-dominant cellular neighborhoods relative to 19del subtype, consistent with a comparatively immune-infiltrated phenotype. In contrast, 19del tumors showed lower T-cell infiltration. TP53 co-mutation was also associated with enhanced CD8 + T-cell infiltration. These cross-sectional findings identify hypothesis-generating spatial immune phenotypes across EGFR-mutant LUAD subtypes; their potential relevance to perioperative treatment selection requires prospective validation in outcome-annotated treatment cohorts.

Humans↗

PubMed2026

Decoding tumor immune microenvironment heterogeneity by single-cell and spatial multi-omics: From immunotherapy resistance to translational biomarkers.

Immune checkpoint blockade has transformed cancer therapy, yet primary and acquired resistance remain major clinical challenges. Increasing evidence indicates that immunotherapy resistance cannot be fully explained by tumor-intrinsic alterations or conventional biomarkers such as PD-L1 expression, tumor mutational burden, or microsatellite instability. Instead, therapeutic response is shaped by the tumor immune microenvironment (TIME) as a heterogeneous, spatially organized, and dynamically evolving ecosystem. Single-cell omics has revealed diverse immune and stromal cell states, including progenitor and terminally exhausted T cells, suppressive myeloid programs, B-cell/TLS-associated immune-reactive states, and CAF-mediated exclusion phenotypes. Spatial transcriptomics, spatial proteomics, and imaging-based approaches further demonstrate that these cell states assemble into distinct immune niches, including immune-inflamed, T-cell-excluded, myeloid-suppressive, metabolic/hypoxic, and TLS-associated niches. These spatial ecosystems determine whether antitumor immune cells can access malignant cells, receive antigen-presenting support, or become restrained by stromal, vascular, metabolic, and myeloid barriers. In this review, we summarize how single-cell and spatial multi-omics redefine TIME heterogeneity in immunotherapy resistance, highlight ligand-receptor communication networks linking cell states to spatial immune dysfunction, and discuss emerging translational biomarkers for patient stratification. We further propose that future immunotherapy biomarkers should evolve from static single-marker assays toward longitudinal, spatially resolved, and interpretable multi-omics models that guide precision combination immunotherapy.

Humans↗

PubMed2026

Targeting Regnase-1 in B7-H3-CAR T cells reprograms the tumor microenvironment and enhances antitumor efficacy for osteosarcoma.

The microenvironment in solid tumors represents an immunosuppressive therapeutic barrier to CAR T cell therapy, and it is currently unknown whether it can be reshaped by the deletion of negative regulators in CAR T cells. To address this knowledge gap, we evaluated the intrinsic and extrinsic effects of deleting the negative regulator Regnase-1 (Reg-1) in B7-H3-CAR T cells for the immunotherapy of osteosarcoma. Reg-1 knockout (KO) improved the antitumor activity of human and murine B7-H3-CAR T cells in vivo. In immune-competent models, Reg-1 KO also endowed murine B7-H3-CAR T cells with the ability to create a proinflammatory landscape characterized by an influx of interferon gamma (IFN-γ)-producing endogenous T cells and natural killer (NK) cells and a reduction of inhibitory myeloid cells, including M2-like macrophages. Thus, deleting Reg-1 has cell- and non-cell-autonomous benefits, nominating Reg-1 KO B7-H3-CAR T cells as a promising cell product for early-phase clinical testing in patients with solid tumors.

Animals↗

PubMed2025

Immune microenvironment in hepatocellular carcinoma: from pathogenesis to immunotherapy.

Hepatocellular carcinoma (HCC) is an increasingly prevalent and deadly disease that is initiated by different etiological factors, such as alcohol-associated liver disease (ALD), metabolic dysfunction-associated steatohepatitis (MASH), viral hepatitis, and other hepatotoxic and hepatocarcinogenic agents. The tumor microenvironment (TME) of HCC is characterized by several different fibroblastic and immune cell types, all of which affect the initiation, progression and metastasis of this malignant cancer. This complex immune TME can be divided into an innate component that includes macrophages, neutrophils, dendritic cells, myeloid-derived suppressor cells, mucosal-associated invariant T cells, natural killer cells, natural killer T cells, and innate lymphoid cells, as well as an adaptive component that includes CD4+ T cells, CD8+ T cells, regulatory T cells, and B cells. In this review, we discuss the latest findings shedding light on the direct or indirect roles of these immune cells (and fibroblastic-like cells such as hepatic stellate cells) in the pathogenesis of HCC. Henceforth, further characterization of this heterogeneous TME is highly important for studying the progression of HCC and developing novel immunotherapeutic treatment options. In line with this, we also review novel groundbreaking experimental techniques and animal models aimed at specifically elucidating this complex TME and discuss emerging immune-based therapeutic strategies intended to treat HCC and predict the efficacy of these immunotherapies.

Humans↗

PubMed2026

Profiling tumor immune microenvironment of epithelial ovarian carcinoma.

BACKGROUND: Epithelial ovarian carcinoma (EOC) comprises five main histological subtypes: high-grade serous (HGSOC), low-grade serous (LGSOC), clear cell (CCOC), mucinous (MOC), and endometrioid (ENOC). Each histotype harbors specific genomic alterations and clinical outcome. Few studies systematically compared the tumor immune microenvironment across the five subtypes. METHODS: We performed 7-plex (CD45, CD8, CD68, CD163, FoxP3, CD20, and cytokeratin) sequential immunohistochemistry on a clinically annotated tissue microarray including 139 EOC representing the five subtypes and 26 borderline tumors (serous and mucinous). Digital pathology was used to quantify immune cell abundance, their spatial distribution (stroma vs tumor core), and correlation with survival. RESULTS: Immune cells were dominated by macrophages and more abundant in the stroma than tumor core across the five subtypes, consistent with immune excluded pattern. Compared to HGSOC, CCOC displayed the highest infiltration by CD45+ leukocytes and CD68+ macrophages, particularly M2-like CD163+ cells, suggesting a macrophage-rich, immunosuppressive phenotype. LGSOC exhibited the highest infiltration by intraepithelial FoxP3+ regulatory T cells. Comparison of borderline tumors with invasive carcinoma (LGOSC and MOC) revealed that malignant progression is accompanied by loss of CD8+ T cells, enrichment in regulatory T cells and increase of CD163+/CD68+ ratio, consistent with immune evasion during tumorigenesis. There was a trend toward better survival in HGSOC highly infiltrated by lymphocytes, either intraepithelial (CD8+ and FoxP3+) or stromal (FoxP3+ and CD20+). CONCLUSIONS: EOC is characterized by histotype-specific immune milieux defined by macrophage dominance, epithelial immune exclusion and dynamic immune remodeling during progression from borderline tumors to invasive carcinomas.

Humans↗

PubMed2025

Exploring prognostic genes in the immune microenvironment of acute myeloid leukemia via weighted gene co-expression network analysis.

BACKGROUND: Acute myeloid leukemia (AML) is a heterogeneous blood cancer that arises from transformed myeloid precursor cells in a compromised bone marrow microenvironment. This environment is essential for AML initiation, progression, and relapse. Alongside oncogenic changes in hematopoietic cells, immunological dysregulation also contributes to leukemogenesis. The present study is aimed to identify prognostic genes in stromal and immune cells associated with AML using the weighted gene co-expression network analysis (WGCNA). METHODS: Gene expression profiles were retrieved from The Cancer Genome Atlas database, and immune and stromal cell scores were calculated using the ESTIMATE (Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data) method. These scores helped identify differentially expressed genes (DEGs), which were then used to create gene clusters through WGCNA. To explore the functions of genes linked to AML subtypes, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed. A protein-protein interaction network was developed to identify hub genes. The top 18 hub genes were identified using the cytoHubba plug-in in Cytoscape software, and survival analysis was conducted with the Gene Expression Profiling Interactive Analysis 2 online tool. RESULTS: A total of 1097 DEGs were identified, with 601 being upregulated and 496 downregulated. WGCNA analysis indicated that the gray module, comprising 165 genes, had the strongest association with AML subtypes (Cor > 0.3; P < .05). Gene Ontology enrichment analysis demonstrated that the 18 identified hub genes were predominantly associated with neutrophil activation, immune response, secretory granule membrane, and pattern recognition receptor activity. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that the DEGs were mainly involved in pathways related to phagosome, lysosome, tuberculosis, leishmaniasis, and neutrophil extracellular trap formation. Kaplan-Meier survival analysis of the top 18 hub genes indicated that ITGAM, IL10, and CD163 were significantly correlated with survival outcomes in AML. CONCLUSION: Key stromal and immune-related genes influencing AML patient outcomes were identified, highlighting their potential as therapeutic targets. These discoveries provide deeper insights into the molecular mechanisms driving AML pathogenesis and subtype differentiation.

Leukemia, Myeloid, Acute↗

PubMed2025

Single-cell spatial mapping reveals alteration of tissue microenvironment during early colorectal cancer.

Familial adenomatous polyposis (FAP) is a rare, hereditary syndrome that raises the risk of developing colorectal cancer (CRC). This disease model is well suited for studying the early stages of malignant transformation. Our spatial CODEX experiments reveal that, in contrast to normal mucosa, FAP mucosa, pre-cancer polyps and colorectal cancers exhibit substantial alterations in the cell type composition and tissue microenvironment. These early alterations include: an increase in the population of cancer-associated fibroblasts (CAFs), and the inhibition of tumor infiltrated lymphocytes and cell-adhesion protein by CAFs, the transformation of memory T cells into regulatory T cells, nuclear translocation of beta-catenin from the cell membrane, a decrease in the M1:M2 macrophage ratio, a notable increase in angiogenesis events. Our studies define the early stem cell, stromal, and immune steps of colorectal cancer and may benefit early detection, and therapeutic intervention.

Co-detection by Indexing (CODEX)↗

PubMed2025

Artificial intelligence-powered spatial analysis of tumor microenvironment in patients with non-small cell lung cancer with acquired resistance to EGFR tyrosine kinase inhibitor.

PURPOSE: This study evaluated the dynamic changes in the tumor microenvironment (TME) in patients with non-small cell lung cancer (NSCLC) and acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) using an artificial intelligence (AI)-powered spatial TME analyzer. We then assessed the predictive efficacy of immune-checkpoint inhibitors (ICIs)-based treatment. EXPERIMENTAL DESIGN: An AI-powered whole-slide image analyzer was used to segment cancer areas (CAs) and cancer stroma and to identify tumor-infiltrating lymphocytes (TILs), tertiary lymphoid structures, fibroblasts, and endothelial cells (ECs) in the tumor tissue. We analyzed 143 NSCLC samples after resistance to EGFR-TKIs from two cohorts: (1) 89 patients treated with ICI monotherapy and (2) 54 patients from the ATTLAS phase III trial comparing atezolizumab plus bevacizumab, paclitaxel, and carboplatin (ABCP) versus pemetrexed plus carboplatin. RESULTS: Post-TKI samples showed reduced TILs in the CA (p=0.045) and increased ECs in the CA (p=0.005) compared with pre-TKI samples. These changes differed according to EGFR mutation subtype. Higher TILs in CA were associated with a better overall response rate (ORR) and progression-free survival (PFS). Similarly, higher EC levels in CA correlated with improved ORR and PFS. In the ATTLAS cohort, these factors were associated with clinical benefits from ABCP, with a significant association with TILs and a marginal association with ECs. CONCLUSION: Our findings suggest that EGFR-TKIs affect the immune landscape of patients with EGFR-mutated NSCLC. Higher TILs or ECs in the CA were significantly associated with a favorable response to subsequent ICI-based treatment. TRIAL REGISTRATION NUMBER: NCT03991403.

Aged↗