The Role of the Immune System in Cutaneous Squamous Cell Carcinoma

Matthew J Bottomley, Jason Thomson, Catherine Harwood, Irene Leigh, Matthew J Bottomley, Jason Thomson, Catherine Harwood, Irene Leigh

Abstract

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer. In immunosuppressed populations it is a source of considerable morbidity and mortality due to its enhanced recurrence and metastatic potential. In common with many malignancies, leucocyte populations are both protective against cancer development and also play a role in 'sculpting' the nascent tumor, leading to loss of immunogenicity and tumor progression. UV radiation and chronic viral carriage may represent unique risk factors for cSCC development, and the immune system plays a key role in modulating the response to both. In this review, we discuss the lessons learned from animal and ex vivo human studies of the role of individual leucocyte subpopulations in the development of cutaneous SCC. We then discuss the insights into cSCC immunity gleaned from studies in humans, particularly in populations receiving pharmacological immunosuppression such as transplant recipients. Similar insights in other malignancies have led to exciting and novel immune therapies, which are beginning to emerge into the cSCC clinical arena.

Keywords: SCC; cSCC; cancer; cutaneous; immunity; immunology; leucocyte; malignancy; skin; squamous cell carcinoma.

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Mechanisms contributing to regulation of tumor clearance by effector cells. APC, antigen presenting cell. In this context, an APC may be a macrophage, dendritic cell (or Langerhans cell) or B cell. Regulatory cells may represent various populations, including Treg, B cell regulatory populations, and myeloid-derived suppressor cells (MDSCs). Effector cell relates predominantly to CD8+ T cells, but may also include natural killer (NK), natural killer T (NKT), gamma-delta T, and cytotoxic CD4+ T cells. The above mechanisms contribute to effector, particularly CD8+, cell dysfunction and lead to a failure of tumor clearance. Those mechanisms highlighted in blue represent mechanisms of immune escape for the tumor. Examples of relevant mediators for each pathway are provided in brackets. Solid arrows represent mechanisms directed against specific cells through cell contact, whilst dashed arrows represent nonspecific mechanisms through remodeling of the tumor microenvironment (TME).

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