The therapeutic and prognostic implications of immunobiology in colorectal cancer: a review

Abstract

Colorectal cancer represents the second leading cause of cancer-related death worldwide. The therapeutic field of immuno-oncology has rapidly gained momentum, with strikingly promising results observed in clinical practice. Increasing emphasis has been placed on the role of the immune response in tumorigenesis, therapy and predicting prognosis. Enhanced understanding of the dynamic and complex tumour-immune microenvironment has enabled the development of molecularly directed, individualised treatment. Analysis of intra-tumoural lymphocyte infiltration and the dichotomisation of colorectal cancer into microsatellite stable and unstable disease has important therapeutic and prognostic implications, with potential to capitalise further on this data. This review discusses the latest evidence surrounding the tumour biology and immune landscape of colorectal cancer, novel immunotherapies and the interaction of the immune system with each apex of the tripartite of cancer management (oncotherapeutics, radiotherapy and surgery). By utilising the synergy of chemotherapeutic agents and immunotherapies, and identifying prognostic and predictive immunological biomarkers, we may enter an era of unprecedented disease control, survivorship and cure rates.

Fig. 1. Activation of CD8+ T cells in the tumour microenvironment, and mechanisms of inhibitory checkpoint blockade.

a Normal cytotoxic elimination of tumour cell. b Expression of inhibitory checkpoint and suppression of T-cell effector function. c Checkpoint blockade and reinvigoration of effector function.

Fig. 2. The immunomodulatory effects of surgery, chemotherapy and radiotherapy.

The various aspects of cancer treament have both immunogenic and immunosuppressive properties.