The interleukin expression pattern relates to cancer associated fibroblasts infiltration and immunotherapy response in pancreatic carcinoma

Abstract Background：Cancer associated fibroblasts (CAFs) and the interleukin (IL) family have been reported to play crucial roles in immune response in pancreatic carcinoma (PC). However, the IL expression pattern and its influence on prognosis, CAFs infiltration characteristics as well as immunotherapy response in PC require further exploration. Methods：An IL family expression pattern that can predict prognosis was constructed using clinical data and meta-analysis of seven independent public cohort datasets. The CAFs infiltration characteristics with prognosis of patients were detected. Correlation between IL expression pattern and CAFs infiltration and immunotherapy response were evaluated in the clinical tissue samples. Results：IL high-risk patients had shorter survival time compared with IL low-risk patients both in our cohort and PC datasets. IL high-risk patients exhibited advanced tumors and lymph node metastasis. IL family–based signature can also serve as predictor of immunotherapy to PC. Patients with unfavorable response to immunotherapy had significantly higher IL risk score than patients with favorable response. The IL family expression pattern can distinguish CAFs infiltration characteristics in PC. The IL high-risk group had more infiltration of CAFs, antigen-presenting CAFs (apCAFs) and inflammatory CAFs (iCAFs). Moreover, IL high-risk group had increased apCAF/tumor cell engagement and apCAF/Tregs engagement, resulting in a suppressed immune response. IL high-risk group also showed crippled T-cell function and B-cell function and significantly greater levels of predictive biomarkers with poor immune response. Conculsions：This study constructed the first IL expression pattern for predicting CAFs infiltration, immunotherapy response, and prognosis among PC patients. This might promote the precise application of immunotherapy and facilitate treatment options for PC.