ArticleClinical cancer research : an official journal of the American Association for Cancer Research2021
Sex-Based Dimorphism of Anticancer Immune Response and Molecular Mechanisms of Immune Evasion.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 103 citations in OpenAlex.
- Comparative Analysis of the Immune Profiles of Women and Men With Hepatocellular Carcinoma.Cancer medicine · 2026Article
- Clinicopathological Factors Influencing PD-L1 Expression and the Effect of Immune Checkpoint Inhibitors on Survival Outcomes in Patients with Gastric Cancer Depending on Sex in a Tertiary Hospital in South Korea.Cancer research and treatment · 2026Article
- Female sex is associated with improved survival after perioperative immunotherapy in resectable non-small cell lung cancer.Journal of thoracic disease · 2026Article
- Radiotherapy in patients with NSCLC developing progressive disease during immune checkpoint inhibition: Abscopal responses and survival.Clinical and translational radiation oncology · 2026Article
- Sex-based molecular and prognostic disparities in pan-cancer: an analysis across the global cohorts.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- Sex Differences in Cancer Immunotherapy-Clinical Evidence and Mechanisms With a Focus on NSCLC.Immunological reviews · 2026Review
- Sex Differences in Lung Immunity.Immunological reviews · 2026Review
- The Immune Biology of the Adrenal Gland Microenvironment and Its Role in Metastatic Progression.International journal of molecular sciences · 2026Review
- Sex-based survival disparities in patients with stage I-III non-small cell lung cancer vary by treatment modality.Frontiers in oncology · 2026Article
- Ultrasound-based deep learning radiomics for the differential diagnosis of benign and malignant subpleural pulmonary lesions.Frontiers in oncology · 2026Article
- Sex and gender-oriented colorectal cancer screening: a consensus study from the AIOM- GISEG working group.Frontiers in oncology · 2026Article
- Age and sex: dual drivers remodeling the anti-tumor immune microenvironment and shaping personalized immuno-oncology.Frontiers in immunology · 2026Review
- Emerging Predictive Biomarkers of Immunotherapy Sensitivity in Patients with Non-Small Cell Lung Cancer.ImmunoTargets and therapy · 2026Review
- Sex-based analysis of first-line immune-based combinations in intermediate/poor-risk papillary, chromophobe, and unclassified renal cell carcinoma: an ARON-1 subanalysis.Frontiers in oncology · 2026Article
- Review
- Review
- Host-related Determinants of Response to Immunotherapy in Non-small Cell Lung Cancer: The Interplay of Body Composition, Metabolism, Sex and Immune Regulation.Current oncology reports · 2025Review
- Heterogeneity of progression-free survival surrogacy by sex in randomized trials testing immunotherapy in non-small cell lung cancer.JNCI cancer spectrum · 2025Article
- Gender and sex interactions are intrinsic components of cancer phenotypes.Nature reviews. Cancer · 2025Review
- Tumour and microenvironment crosstalk in NSCLC progression and response to therapy.Nature reviews. Clinical oncology · 2025Review
8 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
28 authors at 11 institutions in 4 countries.
Funding
Abstract
purposeWe previously demonstrated that sex influences response to immune checkpoint inhibitors. In this article, we investigate sex-based differences in the molecular mechanisms of anticancer immune response and immune evasion in patients with NSCLC. EXPERIMENTAL
designWe analyzed (i) transcriptome data of 2,575 early-stage NSCLCs from seven different datasets; (ii) 327 tumor samples extensively characterized at the molecular level from the TRACERx lung study; (iii) two independent cohorts of 329 and 391 patients, respectively, with advanced NSCLC treated with anti-PD-1/anti-PD-L1 drugs.
resultsAs compared with men, the tumor microenvironment (TME) of women was significantly enriched for a number of innate and adaptive immune cell types, including specific T-cell subpopulations. NSCLCs of men and women exploited different mechanisms of immune evasion. The TME of females was characterized by significantly greater T-cell dysfunction status, higher expression of inhibitory immune checkpoint molecules, and higher abundance of immune-suppressive cells, including cancer-associated fibroblasts, MDSCs, and regulatory T cells. In contrast, the TME of males was significantly enriched for a T-cell-excluded phenotype. We reported data supporting impaired neoantigens presentation to immune system in tumors of men, as molecular mechanism explaining the findings observed. Finally, in line with our results, we showed significant sex-based differences in the association between TMB and outcome of patients with advanced NSCLC treated with anti-PD-1/PD-L1 drugs.
conclusionsWe demonstrated meaningful sex-based differences of anticancer immune response and immune evasion mechanisms, that may be exploited to improve immunotherapy efficacy for both women and men.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.