ArticleCancer discovery2023
Sex-Biased T-cell Exhaustion Drives Differential Immune Responses in Glioblastoma.
Article in Cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
95 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.
- T cell immunity in glioma and potential implications for immunotherapy: A systematic review.Neuro-oncology · 2026Pooled it
- Sex-Biased Immunity: The Hidden Variable in Immuno-oncology.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Review
- Peptide-mediated inhibition of aberrant chaperone-mediated autophagy in pericytes prevents glioblastoma progression through MAPT/tau secretion.Autophagy · 2026Article
- DeepFaceMouse enables scalable prediction of large-scale brain activity from facial dynamics in mice.Cell reports methods · 2026Article
- Article
- The perinecrotic niche of glioblastoma drives tumor-associated macrophage polarization and immunosuppression via podoplanin-mediated CLEC5A activation.The Journal of clinical investigation · 2026Article
- Tumor infiltrating lymphocytes in glioblastoma: immunobiology and translational implications.NPJ precision oncology · 2026Review
- Reduced Tumor Control in Males Can Result from Impaired CD4+ T-cell Help through the CD40L-CD40 Pathway.Cancer immunology research · 2026Article
- The density of tumour infiltrating lymphocytes in oesophago-gastric cancer varies with disease stage, geographical region and treatment: a post hoc analysis of nine phase III clinical trials.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2026Article
- GABA signaling activation drives glioblastoma progression in female mice through myeloid-derived suppressor cells.Nature cancer · 2026Article
- A proteogenomic RNA processing mechanism drives sex differences in meningioma.Research square · 2026Article
- Sex Differences in Colorectal Tumor-Associated T-cell Responses.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2026Article
- T Cell Exhaustion in Cancer Immunotherapy: Heterogeneity, Mechanisms, and Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Gene regulatory network analysis identifies dysregulation of hypoxia pathways as contributing to glioblastoma treatment resistance in females.Biology of sex differences · 2026Article
- Modeling blood-brain barrier-glioblastoma interactions: implications for chemoresistance and therapeutic targeting.Fluids and barriers of the CNS · 2026Review
- Article
- Male-biased Yap1-Cd276/B7-H3 axis for immune evasion in medulloblastoma.Cancer cell · 2026Article
- Article
- Regrowth Patterns in Glioblastoma-Survival and Predictors.Cancer medicine · 2026Article
- DBSCAN applied to EHRs data from patients with glioblastoma clusters patients based on cytosolic Hsp70 protein, sex, and brain subventricular zone.BioData mining · 2026Article
35 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 6 institutions in 1 country.
Funding
Abstract
Sex differences in glioblastoma (GBM) incidence and outcome are well recognized, and emerging evidence suggests that these extend to genetic/epigenetic and cellular differences, including immune responses. However, the mechanisms driving immunologic sex differences are not fully understood. Here, we demonstrate that T cells play a critical role in driving GBM sex differences. Male mice exhibited accelerated tumor growth, with decreased frequency and increased exhaustion of CD8+ T cells in the tumor. Furthermore, a higher frequency of progenitor exhausted T cells was found in males, with improved responsiveness to anti-PD-1 treatment. Moreover, increased T-cell exhaustion was observed in male GBM patients. Bone marrow chimera and adoptive transfer models indicated that T cell-mediated tumor control was predominantly regulated in a cell-intrinsic manner, partially mediated by the X chromosome inactivation escape gene Kdm6a. These findings demonstrate that sex-biased predetermined behavior of T cells is critical for inducing sex differences in GBM progression and immunotherapy response. SIGNIFICANCE: Immunotherapies in patients with GBM have been unsuccessful due to a variety of factors, including the highly immunosuppressive tumor microenvironment in GBM. This study demonstrates that sex-biased T-cell behaviors are predominantly intrinsically regulated, further suggesting sex-specific approaches can be leveraged to potentially improve the therapeutic efficacy of immunotherapy in GBM. See related commentary by Alspach, p. 1966. This article is featured in Selected Articles from This Issue, p. 1949.
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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.