Obstacles Posed by the Tumor Microenvironment to T cell Activity: A Case for Synergistic Therapies

Kristin G. Anderson, Ingunn M. Stromnes, Philip D. Greenberg

Research output: Contribution to journalReview articlepeer-review

382 Scopus citations


T cell dysfunction in solid tumors results from multiple mechanisms. Altered signaling pathways in tumor cells help produce a suppressive tumor microenvironment enriched for inhibitory cells, posing a major obstacle for cancer immunity. Metabolic constraints to cell function and survival shape tumor progression and immune cell function. In the face of persistent antigen, chronic T cell receptor signaling drives T lymphocytes to a functionally exhausted state. Here we discuss how the tumor and its microenvironment influences T cell trafficking and function with a focus on melanoma, and pancreatic and ovarian cancer, and discuss how scientific advances may help overcome these hurdles.

Original languageEnglish (US)
Pages (from-to)311-325
Number of pages15
JournalCancer Cell
Issue number3
StatePublished - Mar 13 2017

Bibliographical note

Funding Information:
Due to the broad scope of this perspective, we apologize for the omission of many primary references. This work was supported by the Chromosome Metabolism and Cancer Training Grant Program (T32 2T32CA009657-26A1 to K.G.A.), a Solid Tumor Translational Research Award (to K.G.A. and P.D.G.), an Irvington Institute Fellowship Program of the Cancer Research Institute (to I.M.S.), the Jack and Sylvia Paul Estate Fund to Support Collaborative Immunotherapy Research (to I.M.S.), the NIH National Cancer Institute (CA018029 and CA033084 to P.D.G.), the Pancreatic Cancer Action Network (16-65-GREE to P.D.G.). P.D.G. is a founder and shareholder of Juno, Therapeutics and a member of its scientific advisory board. This work was supported in part by a grant from Juno, Therapeutics.

Publisher Copyright:
© 2017 Elsevier Inc.


  • T cell dysfunction
  • TME
  • adoptive T cell therapy
  • genetic engineering
  • immunotherapy
  • tumor microenvironment


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