微卫星不稳定性与 CD8+TIL（肿瘤浸润淋巴细胞）对结直肠癌新辅助化疗反应的影响：一项前瞻性观察性研究

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.

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).

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.

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. Colorectal cancer is often treated with surgery and chemotherapy, but not all patients respond the same way. Researchers are looking for biological markers that can predict who is more likely to benefit from treatment. This study examined two such markers: microsatellite instability (MSI), a genetic feature linked to DNA repair defects, and CD8+ tumor-infiltrating lymphocytes (CD8+ TILs), immune cells that can attack cancer cells. We studied 41 patients with colorectal cancer who received chemotherapy before tumor surgery (neoadjuvant chemotherapy) at a hospital in Indonesia. Patients who had already had surgery before starting chemotherapy were excluded, since their response to treatment could not be measured in the same way. MSI status was assessed using molecular testing, and CD8+ TILs were evaluated using immunohistochemical staining; treatment response was measured with standard imaging criteria. Most tumors were microsatellite-stable, and only a few showed MSI. Nearly half of patients had high levels of CD8+ TILs. Patients with high CD8+ TILs were more likely to respond well to chemotherapy and less likely to have advanced, metastatic disease. MSI status, however, was not significantly linked to treatment response or CD8+ TILs levels, likely because so few patients had MSI tumors. These findings suggest that CD8+ TILs may be a useful indicator of how well a patient will respond to treatment and their overall prognosis. Measuring CD8+ TILs could help doctors identify patients most likely to benefit from chemotherapy, supporting more personalized treatment for colorectal cancer.