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Background: CD103+CD8+ tissue-resident memory T (TRM) cells, associated with better overall survival among various malignancies, are thought to activate anti-tumour immune response and affect therapeutic sensitivity including both immunotherapy and adjuvant chemotherapy (ACT). Methods: Totally 650 muscle-invasive bladder cancer (MIBC) patients from three independent cohorts were included in this study for survival and cisplatin-based ACT response analysis. Another public data set consisting of 195 patients from IMvigor210 trial receiving PD-L1 blockade were involved in the assessment of immunotherapeutic response. Fifty-nine fresh tumour tissues were used to evaluate immune infiltration of CD103+CD8+ TRM cells. Results: Patients with high CD103+CD8+ TRM cells infiltration, but not CD8+ T cells, are more likely to benefit from immunotherapy and ACT. The presence of TRM cells is highly associated with an enhanced IFNγ-enriched and T cell-inflamed anti-tumour microenvironment. Elevated CD103+CD8+ TRM cells infiltration correlated with superior ACT response in mismatch repair (MMR), homologous recombination (HR), PIK3CA/AKT and RAS/RAF pathway proficient or histone modification and cell cycle pathway deficient patients. Conclusions: CD103+CD8+ TRM cells played a crucial role in anti-tumour immunity and served as an ideal prognostic biomarker. It could be treated as a superior companion predictor for treatment response to PD-L1 inhibitor and ACT within MIBC patients. [ABSTRACT FROM AUTHOR]

Introduction: This is a prospective, rigorous inquiry into the systemic immune effects of standard adjuvant chemoradiotherapy, for WHO grade 4, glioblastoma. The purpose is to identify peripheral immunologic effects never yet reported in key immune populations, including myeloid-derived suppressor cells, which are critical to the immune suppressive environment of glioblastoma. We hypothesize that harmful immune-supportive white blood cells, myeloid derived suppressor cells, expand in response to conventionally fractionated radiotherapy with concurrent temozolomide, essentially promoting systemic immunity similar what is seen in chronic diseases like diabetes and heart disease., Methods: 16 patients were enrolled in a single-institution, observational, immune surveillance study where peripheral blood was collected and interrogated by flow cytometry and RNAseq. Tumor tissue from baseline assessment was analyzed with spatial proteomics to link peripheral blood findings to baseline tissue characteristics., Results: We identified an increase in myeloid-derived suppressor cells during the final week of a six-week treatment of chemoradiotherapy in peripheral blood of patients that were not alive at two years after diagnosis compared to those who were living. This was also associated with a decrease in CD8 + T lymphocytes that produced IFNγ, the potent anti-tumor cytokine., Discussion: These data suggest that, as in chronic inflammatory disease, systemic immunity is impaired following delivery of adjuvant chemoradiotherapy. Finally, baseline investigation of myeloid cells within tumor tissue did not differ between survival groups, indicating immune surveillance of peripheral blood during adjuvant therapy may be a critical missing link to educate our understanding of the immune effects of standard of care therapy for glioblastoma., Competing Interests: LS: Research Support- GT Medical Technologies. MH: Data Safety Monitoring Board- Parexel and Advarra; Advisory Board- Servier; Speaking Engagement- Novartis. KR: Research Grant- Elekta AB, Accuray; Honoraria- AstraZeneca, Accuray, NCCN; Travel Expenses- Elekta AB, Accuray, Brainlab, Icotec. ASTRO; Unpaid volunteer for the University of Maryland branch of Camp Kesem- Camp Kesem. ML: Research Support- Arbor, BMS, Accuray, Biohaven, Urogen; Consultant-VBI, InCephalo Therapeutics, Merck, Pyramid Bio, Insightec, Biohaven, Sanianoia, Hemispherian, Novocure, Noxxon, InCando, Century Therapeutics, CraniUs, MediFlix, XSense, Stryker; Shareholder- Egret Therapeutics; Patent- Focused radiation + checkpoint inhibitors, local chemotherapy + checkpoint inhibitors, checkpoints for neuro-inflammation; DSMB – Cellularity. LaK: Research support- BMS, Incyte, Novartis, and Novocure; Study steering committee for Novocure. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sloan, Sen, Liu, Doucet, Blosser, Katulis, Kamson, Grossman, Holdhoff, Redmond, Quon, Lim, Eberhart, Pardoll, Hu, Ganguly and Kleinberg.)