The tumor immune microenvironment in gastroenteropancreatic neuroendocrine neoplasms

Wu-Hu Zhang; Wen-Quan Wang; He-Li Gao; Xian-Jun Yu; Liang Liu

doi:10.1016/j.bbcan.2019.188311

The tumor immune microenvironment in gastroenteropancreatic neuroendocrine neoplasms

Biochim Biophys Acta Rev Cancer. 2019 Dec;1872(2):188311. doi: 10.1016/j.bbcan.2019.188311. Epub 2019 Aug 20.

Authors

Wu-Hu Zhang¹, Wen-Quan Wang², He-Li Gao¹, Xian-Jun Yu³, Liang Liu⁴

Affiliations

¹ Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Pancreatic Cancer Institute, Shanghai, China; Pancreatic Cancer Institute, Fudan University, Shanghai, China.
² Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Pancreatic Cancer Institute, Shanghai, China; Pancreatic Cancer Institute, Fudan University, Shanghai, China. Electronic address: wangwenquan@fudanpci.org.
³ Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Pancreatic Cancer Institute, Shanghai, China; Pancreatic Cancer Institute, Fudan University, Shanghai, China. Electronic address: yuxianjun@fudanpci.org.
⁴ Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Pancreatic Cancer Institute, Shanghai, China; Pancreatic Cancer Institute, Fudan University, Shanghai, China. Electronic address: liuliang@fudanpci.org.

PMID: 31442475
DOI: 10.1016/j.bbcan.2019.188311

Abstract

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a group of rare tumors that are increasing in prevalence. The complex tumor immune microenvironment (TIME) plays an important role in tumor development and the response to immunotherapy but is poorly understood. In this review, the components of the TIME are described in detail, including discussion about infiltrating immune cells, the immune checkpoint system, the cytokine and chemokine milieu, and immunomodulatory factors. Moreover, a comparison between TIMEs among different types of GEP-NENs and the interplay among the TIME, tumor cells, and the stromal microenvironment is described. Novel treatment options for GEP-NENs and potential biomarkers for the immune response are also characterized. We provide a comprehensive generalized review of the TIME that can inform GEP-NEN treatment strategies.

Keywords: Biomarkers; Gastroenteropancreatic neuroendocrine neoplasms; Immune checkpoint inhibitors; Immunotherapy; Tumor immune microenvironment.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Antineoplastic Agents, Immunological / therapeutic use
Clinical Trials as Topic
Cytokines / metabolism
Humans
Immunologic Factors / metabolism
Neuroendocrine Tumors / drug therapy
Neuroendocrine Tumors / immunology*
Pancreatic Neoplasms / drug therapy
Pancreatic Neoplasms / immunology*
Stomach Neoplasms / drug therapy
Stomach Neoplasms / immunology*
Tumor Escape
Tumor Microenvironment

Substances

Antineoplastic Agents, Immunological
Cytokines
Immunologic Factors