Host tissue determinants of tumour immunity

Abstract

Although common evolutionary principles drive the growth of cancer cells regardless of the tissue of origin, the microenvironment in which tumours arise substantially differs across various organ sites. Recent studies have established that, in addition to cell-intrinsic effects, tumour growth regulation also depends on local cues driven by tissue environmental factors. In this Review, we discuss how tissue-specific determinants might influence tumour development and argue that unravelling the tissue-specific contribution to tumour immunity should help the development of precise immunotherapeutic strategies for patients with cancer.

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Fig. 1: The cellular and architectural heterogeneity of the tumour microenvironment at distinct cancer sites.
Fig. 2: Cellular contributors to tissue-specific antitumour responses.
Fig. 3: Therapeutic implications of tumour cell-intrinsic and tumour cell-extrinsic factors dependent on tissue specificity.

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Acknowledgements

The laboratory of M.M. is supported by funding from R01 CA154947, R01 CA190400, R01 AI113221, U24 AI118644, U19 AI117873 and U19 AI128949. S.G. is supported by R01 CA224319 and CA190174 grants. The authors thank G. Akturk, A. O. Kamphorst and J. Martin for helpful comments, and S. Maskey for her help with generating figures.

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H.S., R.R., S.G. and M.M. contributed to researching data, discussing content and writing the article. H.S. and M.M. reviewed and edited the manuscript.

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Correspondence to Hélène Salmon or Miriam Merad.

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H.S. receives research funding from Takeda and Genentech. R.R. is an employee of Innate Pharma. S.G. reports consultancy and/or advisory roles for Merck, Neon Therapeutics and OncoMed and research funding from Bristol-Myers Squibb, Genentech, Immune Design, Agenus, Janssen R&D and Pfizer. M.M. receives funding from Regeneron, Takeda, Genentech and Boehringer Ingelheim.

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Glossary

Uveal melanoma

The most common primary cancer of the eye in adults, arising from melanocytes located in the uvea (which comprises the choroid, the ciliary body and the iris).

Peripheral node addressin

(PNAd). A sulfated protein at the surface of high endothelial venules in secondary and tertiary lymphoid tissues that is crucial for the homing of naive and central memory T cells.

Lymphoid neogenesis

The de novo formation of ectopic lymphoid structures within peripheral tissues during chronic inflammation.

Lymphotoxin

A cytokine expressed by lymphoid tissue inducer cells and lymphocytes. In lymphoid neogenesis, lymphotoxin-α (LTα) forms a complex with LTβ to bind to the LTβ receptor on stromal cells, leading to nuclear factor-κB (NF-κB) signalling, which promotes the production of chemokines necessary for T cell and B cell recruitment.

Parabiosis

The surgical union of two organisms leading to the sharing of blood circulation, enabling the assessment of the recruitment and contribution of blood circulating cells to a cellular compartment in a tissue or lesion.

β-blockers

Drugs blocking β-adrenergic signalling on nerve cells, causing blood vessels to relax and dilate; these are commonly used to treat high blood pressure and other cardiac conditions.

Tumour agnostic

Compatible with any tumour type.

Multivalent vaccines

Vaccines designed to immunize against two or more antigens.

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Salmon, H., Remark, R., Gnjatic, S. et al. Host tissue determinants of tumour immunity. Nat Rev Cancer 19, 215–227 (2019). https://doi.org/10.1038/s41568-019-0125-9

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