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Article

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

1
Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan
2
Department of Medical Electrophysiology, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan
3
Department of Blood Transfusion and Transplantation Immunology, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(23), 9081; https://doi.org/10.3390/ijms21239081
Received: 24 October 2020 / Revised: 27 November 2020 / Accepted: 27 November 2020 / Published: 29 November 2020
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. View Full-Text
Keywords: colorectal cancer; deficient mismatch-repair; Tn antigen; immunotherapy; immune checkpoint colorectal cancer; deficient mismatch-repair; Tn antigen; immunotherapy; immune checkpoint
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MDPI and ACS Style

Matsumoto, T.; Okayama, H.; Nakajima, S.; Saito, K.; Nakano, H.; Endo, E.; Kase, K.; Ito, M.; Yamauchi, N.; Yamada, L.; Kanke, Y.; Onozawa, H.; Fujita, S.; Sakamoto, W.; Saito, M.; Saze, Z.; Momma, T.; Mimura, K.; Kono, K. Tn Antigen Expression Defines an Immune Cold Subset of Mismatch-Repair Deficient Colorectal Cancer. Int. J. Mol. Sci. 2020, 21, 9081. https://doi.org/10.3390/ijms21239081

AMA Style

Matsumoto T, Okayama H, Nakajima S, Saito K, Nakano H, Endo E, Kase K, Ito M, Yamauchi N, Yamada L, Kanke Y, Onozawa H, Fujita S, Sakamoto W, Saito M, Saze Z, Momma T, Mimura K, Kono K. Tn Antigen Expression Defines an Immune Cold Subset of Mismatch-Repair Deficient Colorectal Cancer. International Journal of Molecular Sciences. 2020; 21(23):9081. https://doi.org/10.3390/ijms21239081

Chicago/Turabian Style

Matsumoto, Takuro, 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, and Koji Kono. 2020. "Tn Antigen Expression Defines an Immune Cold Subset of Mismatch-Repair Deficient Colorectal Cancer" International Journal of Molecular Sciences 21, no. 23: 9081. https://doi.org/10.3390/ijms21239081

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