Tn Antigen Expression Defines an Immune Cold Subset of Mismatch-Repair Deficient Colorectal Cancer.

Abstract	Colorectal cancer (CRC) cells often express Tn antigen, a tumor-associated truncated immature O-glycan (GalNAcα-O-Ser/Thr) that can promote tumor progression. Immunotherapies against Tn antigen have been developed and are being evaluated in clinical trials. Tn antigen can also be considered a novel immune checkpoint that induces immunosuppressive signaling through glycan-biding lectins to lead effector T cell apoptosis. We evaluated the correlation of Tn antigen expression by immunohistochemistry with mismatch-repair (MMR) status, tumor-infiltrating lymphocytes, tumor cell PD-L1 expression, and clinicopathological characteristics in 507 CRC patients. Although 91.9% of CRCs showed negative or weak Tn antigen staining (Tn-negative/weak), we identified a small subset of CRCs (8.1%) that displayed particularly intense and diffuse distribution of Tn antigen immunoreactivity (Tn-strong) that closely related to deficient MMR (dMMR). Moreover, 40 dMMR CRCs were stratified into 24 Tn-negative/weak dMMR tumors (60.0%) exhibiting dense CD8+ lymphocyte infiltrate concomitant with a high rate of PD-L1 positivity, and 16 Tn-strong dMMR tumors (40.0%) that demonstrated CD8+ T cell exclusion and a lack of PD-L1 expression, which was comparable to those of proficient MMR. Our finding suggests that the immune cold subset of patients with Tn-strong dMMR CRC may be effectively treated with immune checkpoint blockade therapy or cellular immunotherapy targeting Tn antigen.
Authors	Takuro Matsumoto, Hirokazu Okayama, Shotaro Nakajima, Katsuharu Saito, Hiroshi Nakano, Eisei Endo, Koji Kase, Misato Ito, Naoto Yamauchi, Leo Yamada, Yasuyuki Kanke, Hisashi Onozawa, Shotaro Fujita, Wataru Sakamoto, Motonobu Saito, Zenichiro Saze, Tomoyuki Momma, Kosaku Mimura, Koji Kono
Journal	International journal of molecular sciences (Int J Mol Sci) Vol. 21 Issue 23 (Nov 29 2020) ISSN: 1422-0067 [Electronic] Switzerland
PMID	33260328 (Publication Type: Journal Article)
Chemical References	Antigens, Tumor-Associated, Carbohydrate Tn antigen
Topics	Aged Antigens, Tumor-Associated, Carbohydrate (metabolism) Colorectal Neoplasms (immunology, pathology) DNA Mismatch Repair Female Humans Male Middle Aged

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