Cancer Plasticity and The Microenvironment: Implications for Immunity and Therapy Response

Intrinsic plasticity and the ability of cancer cells to alter their phenotype or function can influence, and be influenced by, the tumour microenvironment (TME). This has been shown to play a major role in dormancy, tumour progression and metastatic processes. It also impacts on clonal selection and is implicated in immune evasion, and thus immunotherapy. The cancer cells and the ‘normal’ cells, especially the immune compartment, undergo constant co-evolution and can contribute to ‘shaping’ each other. Like in the tumour, and probably at least in part imposed by it, heterogeneity and plasticity within the tumour microenvironment can often determine treatment outcome. This has been recently exemplified by tumours that are responsive/‘hot’ or resistant/‘cold’ to immunotherapies.

With the recent, unprecedented success of immunotherapeutics in effective treatment of some patients, this crosstalk between the TME and the tumour has become a major focus of research for understanding and exploiting the critical role of the immune system in cancer. Plasticity within the tumour including the TME, can be dictated by various selective pressures including treatment. More recently, other tumour extrinsic factors including the patient’s innate immunity, the extent and duration of inflammation, the balance of the microbiome and even the levels of stress, are also thought to influence patient outcomes. Although these characteristics can contribute to the establishment and/or progression of disease, their influence either directly on the tumour or via the immune system, can impact on treatment response and therapy outcomes. There is an urgent need to personalise immunotherapeutics and identify those that will benefit.

We currently face new challenges for evaluation of effective treatment strategies to accelerate the clinical translation of combination treatments that can improve patient outcomes. This second edition of our Research Topic on cancer cell plasticity will build upon the first edition, Cellular and Phenotypic Plasticity in Cancer, to expand the focus to aspects of immunity and therapy responses across multiple cancer types. It will include some new aspects of cancer plasticity, dormancy and immunity that have recently come to the forefront of cancer research, as we embark on an era of multi-modal therapy, particularly the incorporation of effective immune-modulating drugs in treatment regimens.