The Impact of Microsatellite Instability and CD8+ Tumor Infiltrating Lymphocytes on Neoadjuvant Chemotherapy Response in Colorectal Cancer: A Prospective Observational Study

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Background: Treatment of colorectal cancer includes surgery and chemotherapy, along with advances in personalised therapies, which focus on achieving safer and more effective outcomes. One of the processes underlying colorectal cancer is microsatellite instability (MSI), and CD8+ Tumor Infiltrating Lymphocytes (TILs) belong to the immune cell subset that shows high impact on cancerous cells. The purpose of this study is to determine whether MSI, CD8+ TILs expression, and chemotherapy response are related. Methods: This is a retrospective cohort study of colorectal cancer patients who received chemotherapy in the neoadjuvant setting, prior to tumor resection, at a tertiary general hospital in West Java, Indonesia. The MSI examination was carried out using qPCR-HRM (BioColoMelt-Dx), and the TILs CD8+ expression was carried out using immunohistochemistry. The chemotherapy response was evaluated using response evaluation criteria for solid tumors (RECIST). Results: Forty-one subjects were enrolled in this study. There were three subjects (7.3%) with microsatellite instability (1 MSI-L, 2 MSI-H) and 19 subjects (46.3%) with high CD8+ TILs expression. There were 28 (68.3%) subjects in stage III, followed by stage IV (22%) and stage II (9.8%). There were 10 subjects (24%) who showed progressive disease, and 16 subjects (39%) with high expression of CD8+ TILs showed partial chemotherapy response. MSI showed a significant association with age (P<0.05). The CD8+ TILs expression showed no significant association with sex, subtype, grade, or tumor location, but significantly associated with age, stage and chemotherapy response (P < 0.05). Subjects with MSI tend to have early onset disease. Colorectal cancer with high CD8+ TILs expression was less likely to have metastasis (stage IV) and had a better chemotherapy response when compared to those with low CD8+ TILs expression. Conclusion: The MSI status showed no significant relationship with CD8+ TILs. Patients with high CD8+ TILs showing a relationship with a better chemotherapy response and a better prognosis in colorectal cancer patients.

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