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• W4200569084 abstract "Colorectal cancer (CRC) is one of the most common cancer worldwide, with a growing impact on public health and clinical management. Immunotherapy has shown promise in the treatment of advanced cancers, but needs to be improved for CRC, since only a limited fraction of patients is eligible for treatment, and most of them develop resistance due to progressive immune exhaustion. Here, we identify the transcriptional, molecular, and cellular traits of the immune exhaustion associated with CRC and determine their relationships with the patient's clinic-pathological profile. Bioinformatic analyses of RNA-sequencing data of 594 CRCs from TCGA PanCancer collection, revealed that, in the wide range of immune exhaustion genes, those coding for PD-L1, LAG3 and T-bet were associated (Cramér's V=0.3) with MSI/dMMR tumors and with a shorter overall survival (log-rank test: p=0.0004, p=0.0014 and p=0.0043, respectively), whereas high levels of expression of EOMES, TRAF1, PD-L1, FCRL4, BTLA and SIGLEC6 were associated with a shorter overall survival (log-rank test: p=0.0003, p=0.0188, p=0.0004, p=0.0303, p=0.0052 and p=0.0033, respectively), independently from the molecular subtype of CRC. Expression levels of PD-L1, PD-1, LAG3, EOMES, T-bet, and TIGIT were significantly correlated with each other and associated with genes coding for CD4+ and CD8+CD3+ T cell markers and NKp46+CD94+EOMES+T-bet+ cell markers, (OR >1.5, p<0.05), which identify a subset of group 1 innate lymphoid cells, namely conventional (c)NK cells. Expression of TRAF1 and BTLA co-occurred with both T cell markers, CD3γ, CD3δ, CD3ε, CD4, and B cell markers, CD19, CD20 and CD79a (OR >2, p<0.05). Expression of TGFβ1 was associated only with CD4+ and CD8+CD3ε+ T cell markers (odds ratio >2, p<0.05). Expression of PD-L2 and IDO1 was associated (OR >1.5, p<0.05) only with cNK cell markers, whereas expression of FCRL4, SIGLEC2 and SIGLEC6 was associated (OR >2.5; p<0.05) with CD19+CD20+CD79a+ B cell markers. Morphometric examination of immunostained CRC tissue sections, obtained from a validation cohort of 53 CRC patients, substantiated the biostatistical findings, showing that the highest percentage of immune exhaustion gene expressing cells were found in tumors from short-term survivors and that functional exhaustion is not confined to T lymphocytes, but also involves B cells, and cNK cells. This concept was strengthened by CYBERSORTx analysis, which revealed the expression of additional immune exhaustion genes, in particular FOXP1, SIRT1, BATF, NR4A1 and TOX, by subpopulations of T, B and NK cells. This study provides novel insight into the immune exhaustion landscape of CRC and emphasizes the need for a customized multi-targeted therapeutic approach to overcome resistance to current immunotherapy." @default.
• W4200569084 created "2021-12-31" @default.
• W4200569084 creator A5000626730 @default.
• W4200569084 creator A5023681297 @default.
• W4200569084 creator A5059575143 @default.
• W4200569084 creator A5086188675 @default.
• W4200569084 creator A5090347980 @default.
• W4200569084 date "2021-12-16" @default.
• W4200569084 modified "2023-10-17" @default.
• W4200569084 title "Colorectal Cancer-Associated Immune Exhaustion Involves T and B Lymphocytes and Conventional NK Cells and Correlates With a Shorter Overall Survival" @default.
• W4200569084 cites W1479904733 @default.
• W4200569084 cites W1567241199 @default.
• W4200569084 cites W1595770568 @default.
• W4200569084 cites W171251970 @default.
• W4200569084 cites W1910012553 @default.
• W4200569084 cites W1965288495 @default.
• W4200569084 cites W1969950463 @default.
• W4200569084 cites W1971907885 @default.
• W4200569084 cites W1973680986 @default.
• W4200569084 cites W1976507542 @default.
• W4200569084 cites W1978019219 @default.
• W4200569084 cites W1984642649 @default.
• W4200569084 cites W1985987855 @default.
• W4200569084 cites W1986269759 @default.
• W4200569084 cites W1987962124 @default.
• W4200569084 cites W1997241837 @default.
• W4200569084 cites W2000680502 @default.
• W4200569084 cites W2010463731 @default.
• W4200569084 cites W2013013791 @default.
• W4200569084 cites W2029349480 @default.
• W4200569084 cites W2034000134 @default.
• W4200569084 cites W2039123767 @default.
• W4200569084 cites W2042797183 @default.
• W4200569084 cites W2043416239 @default.
• W4200569084 cites W2046762204 @default.
• W4200569084 cites W2060070314 @default.
• W4200569084 cites W2061300591 @default.
• W4200569084 cites W2066090902 @default.
• W4200569084 cites W2066118264 @default.
• W4200569084 cites W2070311659 @default.
• W4200569084 cites W2073504276 @default.
• W4200569084 cites W2077116159 @default.
• W4200569084 cites W2082431132 @default.
• W4200569084 cites W2091794422 @default.
• W4200569084 cites W2092547986 @default.
• W4200569084 cites W2094390470 @default.
• W4200569084 cites W2095808484 @default.
• W4200569084 cites W2109400604 @default.
• W4200569084 cites W2116171543 @default.
• W4200569084 cites W2118471749 @default.
• W4200569084 cites W2119064369 @default.
• W4200569084 cites W2135497573 @default.
• W4200569084 cites W2141649749 @default.
• W4200569084 cites W2145449065 @default.
• W4200569084 cites W2146914242 @default.
• W4200569084 cites W2147605136 @default.
• W4200569084 cites W2147787458 @default.
• W4200569084 cites W2155356620 @default.
• W4200569084 cites W2161479825 @default.
• W4200569084 cites W2165920582 @default.
• W4200569084 cites W2169653318 @default.
• W4200569084 cites W2283867425 @default.
• W4200569084 cites W2323626307 @default.
• W4200569084 cites W2342494521 @default.
• W4200569084 cites W2397739282 @default.
• W4200569084 cites W2403400382 @default.
• W4200569084 cites W2462014591 @default.
• W4200569084 cites W2470575266 @default.
• W4200569084 cites W2531883437 @default.
• W4200569084 cites W2542352674 @default.
• W4200569084 cites W2553172239 @default.
• W4200569084 cites W2591704778 @default.
• W4200569084 cites W2591817769 @default.
• W4200569084 cites W2611212932 @default.
• W4200569084 cites W2618063318 @default.
• W4200569084 cites W2741119937 @default.
• W4200569084 cites W2752502706 @default.
• W4200569084 cites W2753621408 @default.
• W4200569084 cites W2786095824 @default.
• W4200569084 cites W2788975052 @default.
• W4200569084 cites W2791048627 @default.
• W4200569084 cites W2791423447 @default.
• W4200569084 cites W2792405992 @default.
• W4200569084 cites W2796153844 @default.
• W4200569084 cites W2801637031 @default.
• W4200569084 cites W2803164733 @default.
• W4200569084 cites W2808601843 @default.
• W4200569084 cites W2889169377 @default.
• W4200569084 cites W2889646458 @default.
• W4200569084 cites W2890862599 @default.
• W4200569084 cites W2892910119 @default.
• W4200569084 cites W2903754922 @default.
• W4200569084 cites W2911188335 @default.
• W4200569084 cites W2911574559 @default.
• W4200569084 cites W2912648593 @default.
• W4200569084 cites W2916738215 @default.
• W4200569084 cites W2941436323 @default.
• W4200569084 cites W2942610007 @default.
• W4200569084 cites W2942750823 @default.
• W4200569084 cites W2944181742 @default.

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