3146 - Oncopathological Study on Radiation-Induced Anti-Tumor Immunity in Pancreatic Cancer Treated with Neoadjuvant Chemoradiotherapy

Purpose/Objective(s): The prognosis of pancreatic cancer (PC) remains very poor despite multimodal therapeutic approaches. Neoadjuvant chemoradiotherapy (NACRT) is used in PC to improve surgical margins and reduce tumor micrometastasis. Emerging evidence in other malignancies suggests that chemoradiotherapy may potentiate immunotherapy by modulating immune checkpoint expression, lymphocyte infiltration and antigen presentation pathways. This study investigates whether NACRT induces immunogenic changes in PC using immunohistochemistry.

Materials/Methods: Twenty-four and 62 patients were included in the NACRT and surgery alone cohorts, respectively. Immunohistochemical staining was used to visualize the number of tumor-infiltrating CD8+ T cells (TILs) and the expression levels of human leukocyte antigen (HLA) class I and programmed death ligand 1 (PD-L1) on the tumor cell membrane. To evaluate TILs, hotspot areas were selected and the mean number of stained lymphocytes across four areas was calculated. HLA class I expression was assessed by scoring based on the percentage of positivity: 0 (0%), 1 (1%-9%), 2 (10%-49%), 3 (50%-79%) and 4 (>80%). PD-L1 was considered positive if >1% of tumor cells were positive.

Results: For clinical tumor staging (staging before NACRT or surgery), the numbers of T1/T2 and T3 were 5 and 19 in the NACRT cohort and 25 and 37 in the surgery alone cohort. Meanwhile, for pathological tumor staging (staging by surgically resected tissue), the numbers of T1/T2 and T3 were 11 and 13 in the NACRT cohort and 7 and 55 in the surgery alone cohort. A statistically significant difference was observed between the cohorts (p=0.01), indicating that NACRT had anti-tumor effects. The median number of TILs was 63.88 (95% CI: 44.0-91.25) in the NACRT group and 53.75 (95% CI: 46.5-65.75) in the surgery alone group. The median HLA class I expression was +2.0 (95% CI 2.24-2.70) in the NACRT group and 2.0 (95% CI 1.78-2.64) in the surgery-alone group. There were no significant differences between the NACRT cohort and the surgery alone cohort for the mean number of TILs and HLA class ? expression (p = 0.11 and p = 0.33, respectively). PD-L1 expression was detected in only 2 patients in both the NACRT and surgery alone cohorts (8% and 3%), with no significant difference (P = 0.31).

Conclusion: There was no significant difference in the degree of TILs and the expression of HLA class I and PD-L1 between the NACRT cohort and the surgery alone cohort of PC.