Targeting tumor immunosuppressive microenvironment for pancreatic cancer immunotherapy: Current research and future perspective

Ying Li; Shuai Xiang; Wenjun Pan; Jing Wang; Hanxiang Zhan; Shanglong Liu

doi:10.3389/fonc.2023.1166860

Targeting tumor immunosuppressive microenvironment for pancreatic cancer immunotherapy: Current research and future perspective

Front Oncol. 2023 Mar 29:13:1166860. doi: 10.3389/fonc.2023.1166860. eCollection 2023.

Authors

Ying Li¹, Shuai Xiang², Wenjun Pan², Jing Wang³, Hanxiang Zhan⁴, Shanglong Liu²

Affiliations

¹ Department of Blood Transfusion, the Affiliated Hospital of Qingdao University, Qingdao, China.
² Department of Gastrointestinal Surgery, the Affiliated Hospital of Qingdao University, Qingdao, China.
³ Department of Operating Room, the Affiliated Hospital of Qingdao University, Qingdao, China.
⁴ Department of General Surgery, Qilu hospital, Shandong University, Jinan, Shandong, China.

Abstract

Pancreatic cancer is one of the most malignant tumors with increased incidence rate. The effect of surgery combined with chemoradiotherapy on survival of patients is unsatisfactory. New treatment strategy such as immunotherapy need to be investigated. The accumulation of desmoplastic stroma, infiltration of immunosuppressive cells including myeloid derived suppressor cells (MDSCs), tumor associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), and regulatory T cells (Tregs), as well as tumor associated cytokine such as TGF-β, IL-10, IL-35, CCL5 and CXCL12 construct an immunosuppressive microenvironment of pancreatic cancer, which presents challenges for immunotherapy. In this review article, we explore the roles and mechanism of immunosuppressive cells and lymphocytes in establishing an immunosuppressive tumor microenvironment in pancreatic cancer. In addition, immunotherapy strategies for pancreatic cancer based on tumor microenvironment including immune checkpoint inhibitors, targeting extracellular matrix (ECM), interfering with stromal cells or cytokines in TME, cancer vaccines and extracellular vesicles (EVs) are also discussed. It is necessary to identify an approach of immunotherapy in combination with other modalities to produce a synergistic effect with increased response rates in pancreatic cancer therapy.

Keywords: clinical trial; immunosuppression; immunotherapy; pancreatic cancer; tumor microenvironment.

Publication types

Review

Grants and funding

The study was supported by the National Natural Science Foundation of China (Grant No. 81802888), the Key Research and Development Program of Shandong (No. 2018GSF118088), and the General Financial Grant from the China Postdoctoral Science Foundation (No. 2016M592143).