Genetic and epigenetic regulation of cancer-associated glycan truncation in colorectal cancer

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09151
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Fukushima Medical University
• Principal Investigator: Hirokazu Okayama 福島県立医科大学, 医学部, 講師 (20583397)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 大腸癌 / 糖鎖 / Tn抗原

Outline of Final Research Achievements

Colorectal cancer (CRC) cells often express a tumor-associated truncated immature O-glycan, Tn antigen. It has recently been proposed that Tn antigen can also be considered a novel immune checkpoint that induces immunosuppressive signaling through glycan-biding lections to lead effector T cell apoptosis. We here examined the expression of Tn antigen by immunohistochemistry in more than 500 CRCs and adenomas. We identified a small subset of CRCs displaying strong Tn antigen immunoreactivity that closely related to deficient MMR (dMMR). Moreover, Tn-Strong/dMMR tumors demonstrated low infiltration of CD8+ T cell and low levels of PD-L1 expression. Our finding suggests that the Tn-Strong-dMMR CRC may be treated with immunotherapeutic strategies targeting Tn antigen.

Free Research Field

大腸癌

Academic Significance and Societal Importance of the Research Achievements

大腸癌、特にdMMR大腸癌において腫瘍免疫の抑制に重要な役割を果たすことが示唆されるTn抗原についてその臨床的意義を解明することは、大腸癌の進展や腫瘍免疫の生物学的機構を理解するために重要であり、または大腸癌治療の個別化にも寄与しうると考える。