Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Expression Patterns of Immune Checkpoint Molecules in Colorectal Cancer: An Analysis Based on Microsatellite Status

Sanghyun An
ORCID logo ,
Wanlu Li
,
Hyejin Do
,
Hye Youn Kwon
,
Bora Kim
,
Kwangmin Kim
ORCID logo ,
Youngwan Kim
* ,
Mee-Yon Cho
* ORCID logo
Version 1 : Received: 20 February 2024 / Approved: 21 February 2024 / Online: 21 February 2024 (15:00:37 CET)

A peer-reviewed article of this Preprint also exists.

An, S.; Li, W.; Do, H.; Kwon, H.Y.; Kim, B.; Kim, K.; Kim, Y.; Cho, M.-Y. The Expression Patterns of Immune Checkpoint Molecules in Colorectal Cancer: An Analysis Based on Microsatellite Status. Biomedicines 2024, 12, 752. An, S.; Li, W.; Do, H.; Kwon, H.Y.; Kim, B.; Kim, K.; Kim, Y.; Cho, M.-Y. The Expression Patterns of Immune Checkpoint Molecules in Colorectal Cancer: An Analysis Based on Microsatellite Status. Biomedicines 2024, 12, 752.

Abstract

Recently, immunotherapy has arisen as a novel treatment approach for patients with colorectal cancer (CRC), but the effectiveness of immunotherapy varies in these patients. We hypothesized that immune checkpoint molecules (ICMs), which are the targets of immunotherapy, are often exhibit concomitantly. Our objective was to investigate the patterns of ICM expression in patients with CRC and the differences in ICM expression based on the microsatellite instability status. Immunohistochemical expression of programmed cell death protein 1 (PD-1), programmed cell death ligand 1 (PD-L1), T cell immunoglobulin and mucin-domain containing-3 (TIM-3), and lymphocyte-activation gene 3 (LAG-3) in the tumor center and periphery was assessed in patients with non-metastatic colorectal cancer. We enrolled 83 patients with CRC: 40 with microsatellite stable (MSS) and 43 with microsatellite instability-high (MSI-H). PD-L1 was more frequently expressed in the tumor center in patients with MSI-H than that in patients with MSS (18 [41.9 %] vs. 3 [7.5 %], respectively; P < 0.001), and the same trend was observed for TIM-3 expression (30 [69.8 %] vs. 19 [47.5 %], respectively; P = 0.047). Concomitant expression of two or more ICMs was more frequently observed than no expression or expression of a single molecule in both MSS and MSI-H groups; 34 (79.7 %) patients with MSI-H and 23 (57.5 %) with MSS showed ICM expression at the tumor center, whereas 34 (79.7 %) patients with MSI-H and 22 (55 %) with MSS showed expression at the tumor periphery. Patients with the genetic characteristics of MSI-H showed higher expression levels of ICMs than that in patients with MSS, and predominantly, two or more ICMs were concurrently expressed. Our findings highlight the potential efficacy of the dual-blockade approach in immunotherapy, particularly in patients with MSI-H CRC.

Keywords

colorectal neoplasms; microsatellite instability; immune checkpoint proteins; immunotherapy

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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