Relevance of Immune Infiltration and Clinical Outcomes in Pancreatic Ductal Adenocarcinoma Subtypes

Rong Liu; Ya-Zhou Liao; Wei Zhang; Hong-Hao Zhou

doi:10.3389/fonc.2020.575264

Relevance of Immune Infiltration and Clinical Outcomes in Pancreatic Ductal Adenocarcinoma Subtypes

Front Oncol. 2021 Jan 6:10:575264. doi: 10.3389/fonc.2020.575264. eCollection 2020.

Authors

Rong Liu^{1

2

3

4}, Ya-Zhou Liao⁵, Wei Zhang^{1

2

3

4}, Hong-Hao Zhou^{1

2

3

4}

Affiliations

¹ Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.
² Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, China.
³ Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, China.
⁴ National Clinical Research Center for Geriatric Disorders, Changsha, China.
⁵ Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya Hospital, Central South University, Changsha, China.

Abstract

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with high heterogeneity and dismal survival rates. Tumor immune microenvironment plays a critical role in sensitive to chemotherapy and prognosis. Herein, we determined the relevance of the composition of tumor-infiltrating immune cells to clinical outcomes in PDACs, and we evaluated these effects by molecular subtype.

Experimental design: Data of 1,274 samples from publically available datasets were collected. Molecular subtypes were predicted with support vector machine. Twenty-two subsets of immune cells were estimated with CIBERSORTx. The associations between each cell subset and overall survival (OS), relapse free survival (RFS), and complete response (CR) to chemotherapy were evaluated, modelling cellular proportions as quartiles.

Results: An immune-related cluster was identified with unsupervised hierarchical clustering of hallmark pathways. Of the immune cells investigated, M0 macrophages emerged as closely associated with worse OS (HR =1.23, 95% CI = 1.15-1.31, p=1.57×10^-9) and RFS (HR = 1.14, 95% CI =1.04-1.25, p=2.93×10^-3), regardless of molecular subtypes. The CD8+ T cells conferred favorable survival. The neutrophils conferred poor OS overall (HR=1.17, 95% CI=1.10-1.23, p=1.74×10^-7) and within the classical subtype. In the basal-like subtype, activated mast cells were associated with worse OS. Consensus clustering revealed six immune subgroups with distinct survival patterns and CR rates. The higher expression of PD1 was associated with better OS.

Conclusions: The immune cellular composition infiltrate in PDAC are likely to have effects on prognosis. Further exploration of the cellular immune response has the potential to identify candidates for immunotherapy.

Keywords: M0 macrophages; overall survival; pancreatic ductal adenocarcinoma; relapse free survival; tumor-immune infiltration.