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• W4385578329 abstract "<div>Abstract<p>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 <i>Kdm6a.</i> These findings demonstrate that sex-biased predetermined behavior of T cells is critical for inducing sex differences in GBM progression and immunotherapy response.</p>Significance:<p>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.</p></div>" @default.
• W4385578329 created "2023-08-05" @default.
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• W4385578329 date "2023-08-04" @default.
• W4385578329 modified "2023-09-23" @default.
• W4385578329 title "Data from Sex-Biased T-cell Exhaustion Drives Differential Immune Responses in Glioblastoma" @default.
• W4385578329 doi "https://doi.org/10.1158/2159-8290.c.6775717.v1" @default.
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