Development of a Nomogram Integrating Immune Checkpoints, 1 Fibrosis indicators, and Clinicopathological Characteristics to 2 Predict Overall Survival in Pancreatic Cancer: A Retrospective 3 Analysis

Dailei Qin¹Kewei Huang²Zehui Yao¹Lingmin Jiang¹Qi Zhu¹Jianzhong Cao^1*Shengping Li^1*

• ¹State Key Laboratory of Oncology in South China, Department of Hepatobiliary and Pancreatic Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
• ²State Key Laboratory of Oncology in South China, Department of Clinical Laboratory Medicine, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China

Abstract 24 Background: Pancreatic cancer (PC) remains a highly aggressive disease with 25 a poor postoperative 5-year survival of around 25%, attributable to its 26 immunosuppressive and fibrotic tumor microenvironment. Prognostic models 27 that combine immune checkpoint markers with fibrotic features are still needed. 28 Methods: We analyzed qualifying surgically resected PC specimens. 29 Immunohistochemistry was used to evaluate PD-L1, CTLA-4, and α-SMA 30 expression. Extracellular matrix volume (ECV) at the tumor center (ECVC) and 31 peritumoral region (ECVP) was measured by three radiologists using single-32 energy CT. Collagen fraction (CF) was assessed via Masson's trichrome 33 staining. Multivariate Cox regression identified independent predictors of 34 overall survival (OS); a prognostic nomogram was then developed. 35 Results: Among 268 enrolled patients, divided into training (n=215) and 36 validation (n=53) sets via Five-fold cross-validation, PD-L1 expression 37 correlated positively with α-SMA, T stage, and N stage. Multivariate analysis 38 identified α-SMA H-score, Masson-CF, ECVC, ECVP, T stage, N stage, CA19-39 9, neutrophil-to-lymphocyte ratio (NLR), vascular invasion, and chemotherapy 40 as independent OS predictors. The nomogram integrating these factors 41 outperformed TNM staging in predicting OS. 42 Conclusion: 43 High PD-L1 expression is associated with enhanced fibrosis, greater tumor 44 burden, and nodal metastasis in PC. Patients exhibiting elevated PD-L1 levels, 45 significant fibrotic burden, advanced T or N stage, or increased NLR 46 demonstrate reduced OS. The developed nomogram enhances individualized 47 prediction of OS. These findings support the hypothesis that combining immune 48 checkpoint blockade, TGF-β inhibition, and chemotherapy may represent a 49 promising therapeutic strategy for PC patients with high PD-L1 expression and 50 pronounced fibrosis.