Clinical relevance of host immunity in breast cancer: from TILs to the clinic

Key Points

  • The detection of tumour-infiltrating lymphocytes (TILs) on routine histology constitutes a robust prognostic and predictive biomarker in patients with early stage breast cancer, despite the complexity of host antitumour immunity

  • Ongoing efforts to ensure reliable and reproducible reporting of TILs will facilitate their use in the routine management of breast cancer

  • Exploiting the antitumour immune response in breast cancer for therapeutic benefit is currently an area of active research

  • Early phase trials of antibodies that target programmed cell-death protein 1 (PD-1) and PD1 ligand 1 in patients with metastatic triple-negative breast cancer have shown promising and durable responses

  • Useful biomarkers to predict benefit from immunotherapy are urgently needed — TILs might fulfil this role

Abstract

The clinical relevance of the host immune system in breast cancer has long been unexplored. Studies developed over the past decade have highlighted the biological heterogeneity of breast cancer, prompting researchers to investigate whether the role of the immune system in this malignancy is similar across different molecular subtypes of the disease. The presence of high levels of lymphocytic infiltration has been consistently associated with a more-favourable prognosis in patients with early stage triple-negative and HER2-positive breast cancer. These infiltrates seem to reflect favourable host antitumour immune responses, suggesting that immune activation is important for improving survival outcomes. In this Review, we discuss the composition of the immune infiltrates observed in breast cancers, as well as data supporting the clinical relevance of host antitumour immunity, as represented by lymphocytic infiltration, and how this biomarker could be used in the clinical setting. We also discuss the rationale for enhancing immunity in breast cancer, including early data on the efficacy of T-cell checkpoint inhibition in this setting.

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Figure 1: Diagram of the immune microenvironment in breast cancer.
Figure 2: Possible trial design using tumour-infiltrating lymphocytes as a biomarker.

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Acknowledgements

The work of S.L. is supported by the Cancer Council Victoria, the National Breast Cancer Foundation (NBCF) Australia, the Breast Cancer Research Foundation (BCRF), New York, and the National Health and Medical Council of Australia (NHMRC). The work of P.S. is supported by the NHMRC. The work of C.D. is supported by the German Cancer Consortium (DKTK), as well as the European Commission (FP7, RESPONSIFY project and TRANSCAN UGI1 project). The work of M.J.S. is supported by the NHMRC and a Susan Komen for the Cure Grant. The work of P.K.D. is supported by an NHMRC Senior Research Fellowship

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P.S., R.S., C.D. and S.L. researched data for the article. P.S., R.S., C.D., P.K.D., M.J.S. and S.L. contributed to discussing the article's content. All authors wrote, reviewed and edited the manuscript before submission.

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Correspondence to Sherene Loi.

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S.L. receives research support from Merck, Novartis, Pfizer and Roche-Genentech, and co-chairs the PANACEA and BOSTON-II studies. M.J.S. has received research support from Bristol-Myers Squibb, and is a consultant for Amgen, F-star and Kymab. C.D. is the cofounder and shareholder of Sividon Diagnostics, Cologne, Germany. The other authors declare no competing interests.

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Savas, P., Salgado, R., Denkert, C. et al. Clinical relevance of host immunity in breast cancer: from TILs to the clinic. Nat Rev Clin Oncol 13, 228–241 (2016). https://doi.org/10.1038/nrclinonc.2015.215

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