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

Prapanca Nugraha,1 Yunia Sribudiani,2 Reno Rudiman,1 Susanti Susanti,3 Hermin Aminah Usman,4 Afrida Helen,5 Etis Primastari,6 Bambang Am Am Setya Sulthana,7 Raden Yohana Azhar,7 Kiki Lukman11Department of Surgery, Faculty of Medicine of Universitas Padjadjaran, Bandung, West Java, Indonesia; 2Department of Biomedical Sciences, Faculty of Medicine of Universitas Padjadjaran, Bandung, West Java, Indonesia; 3Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy of Universitas Muhammadiyah Purwokerto, Purwokerto, Central Java, Indonesia; 4Department of Anatomical Pathology, Faculty of Medicine of Universitas Padjadjaran, Bandung, West Java, Indonesia; 5Department of Computer Science, Faculty of Mathematics and Natural Sciences of Universitas Padjadjaran, Bandung, West Java, Indonesia; 6Department of Anatomical Pathology, Hasan Sadikin General Hospital, Bandung, West Java, Indonesia; 7Department of Surgery, Hasan Sadikin General Hospital, Bandung, West Java, IndonesiaCorrespondence: Kiki Lukman, Email kiki.lukman@unpad.ac.idBackground: 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.Keywords: chemotherapy, colorectal cancer, tumor-infiltrating lymphocytes, MSI