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Review
. 2019 Apr;120(9):871-882.
doi: 10.1038/s41416-019-0441-6. Epub 2019 Apr 2.

Harnessing the innate immune system and local immunological microenvironment to treat colorectal cancer

Jakob Nikolas Kather  1   2   3 , Niels Halama  4   5   6   7
Affiliations
Review

Harnessing the innate immune system and local immunological microenvironment to treat colorectal cancer

Jakob Nikolas Kather et al. Br J Cancer. 2019 Apr.

Abstract

Significant progress in the development of new immunotherapies has led to successful clinical trials for malignant melanoma and non-small cell lung cancer; however, for the majority of solid tumours of the gastrointestinal tract, little or no progress has been seen. The efficacy of immunotherapies is limited by the complexities of a diverse set of immune cells, and interactions between the tumour cells and all other cells in the local microenvironment of solid tumours. A large fraction of immune cells present in and around solid tumours derive from the innate arm of the immune system and using these cells against tumours offers an alternative immunotherapeutic option, especially as current strategies largely harness the adaptive arm of the immune system. This option is currently being investigated and attempts at using the innate immune system for gastrointestinal cancers are showing initial results. Several important factors, including cytokines, chemotherapeutics and the microbiome, influence the plasticity and functionality of innate (myeloid) cells in the microenvironment, and this complexity of regulation has limited translation into successful trials so far. In this review, current concepts of the immunobiology of the innate arm in the tumour microenvironment are presented in the context of clinical translation.

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Conflict of interest statement

The authors declare that there is a conflict of interest. NH holds intellectual property on the use of CCR5 Inhibition in the Treatment of cancer and is a subject editor at the British Journal of Cancer.

Figures

Fig. 1
Fig. 1
Overview of the composition of the immunological microenvironments in different lesions (primary vs. lung and liver metastases) of colorectal cancer (CRC). The pie charts provide examples of immune cell composition within the local microenvironment (data from Halama et al.) to highlight organ-specific heterogeneity. The lower panel provides an overview of the key immune cells that are present in the immunological microenvironment
Fig. 2
Fig. 2
Macrophage cell plasticity also translates to functional plasticity. Functionally relevant signals from within the microenvironment can influence whether macrophages adopt an anti-tumour type I (M1) phenotype or an immunosuppressive type II (M2) phenotype, or any intermediary complex phenotype. Different combinations of these signals can further dynamically affect macrophage differentiation and functionality
See this image and copyright information in PMC

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