Review Article

Impact of oncogenic pathways on evasion of antitumour immune responses

  • Nature Reviews Cancer volume 18, pages 139147 (2018)
  • doi:10.1038/nrc.2017.117
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Abstract

Immunotherapeutic interventions are showing effectiveness across a wide range of cancer types, but only a subset of patients shows clinical response to therapy. Responsiveness to checkpoint blockade immunotherapy is favoured by the presence of a local, CD8+ T cell-based immune response within the tumour microenvironment. As molecular analyses of tumours containing or lacking a productive CD8+ T cell infiltrate are being pursued, increasing evidence is indicating that activation of oncogenic pathways in tumour cells can impair induction or execution of a local antitumour immune response. This Review summarizes our current knowledge of the influence of oncogenic effects on evasion of antitumour immunity.

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Acknowledgements

S.S. was supported by the National Cancer Institute K99/R00CA204595 transition grant. T.F.G. was supported by R35 CA210098 and the American Cancer Society-Jules L. Plangere Jr. Family Foundation Professorship in Cancer Immunotherapy.

Author information

Affiliations

  1. The Koch Institute for Integrative Cancer Research at MIT and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.

    • Stefani Spranger
  2. Department of Pathology, University of Chicago.

    • Thomas F. Gajewski
  3. Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA.

    • Thomas F. Gajewski

Authors

  1. Search for Stefani Spranger in:

  2. Search for Thomas F. Gajewski in:

Contributions

S.S. and T.F.G. researched data for the article, made substantial contributions to discussions of the content, wrote the article and reviewed and/or edited the manuscript before submission.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Stefani Spranger or Thomas F. Gajewski.

Glossary

Checkpoint blockade therapy

Includes all therapies targeting immune inhibitory molecules or pathways mediating a decrease of T cell function within the tumour microenvironment. The most prominent examples are anti- cytotoxic T lymphocyte antigen 4 (CTLA4) and anti-programmed death receptor 1 (PD1) antibodies.

T cell-inflamed

A microenvironment in which CD8+ T cells are found within the tumour mass or the invasive margin of the tumour. T cells produce interferon γ (IFNγ) and other cytokines yet at the same time express immune inhibitory molecules on their surface, including programmed death receptor 1 (PD1).

Non-T cell-inflamed

A microenvironment that is representative of all tumour microenvironments with no evidence of an ongoing CD8+ T cell-driven immune response and lack of expression of key chemokines and cytokines. This group of tumours might be quite diverse.

Basic leucine zipper transcriptional factor ATF-like 3 lineage dendritic cells

(BATF3 DCs). Cells defined by the expression of the transcription factors BATF3 and interferon regulatory factor 8 (IRF8). In mice, they express lineage markers CD8α and/or CD103 (also known as ITGAE), while in humans, they express thrombomodulin (TM; also known as CD141). This lineage of DCs has the capability to cross-present tumour-derived antigens to CD8+ T cells.

Oncogenic pathways

Tumour cell-intrinsic signalling pathways with a known capability to mediate tumour induction or progression from within the tumour cells themselves. They are often but not always associated with specific mutations in oncogenes or tumour suppressor genes.