The Role of the Immune System in Cutaneous Squamous Cell Carcinoma

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.

The Role of Beta HPV Types and HPV-Associated Inflammatory Processes in Cutaneous Squamous Cell Carcinoma

“…Moreover, HPV seems to induce alterations in NK cells that participate in chronic latent viral infections. Certain subpopulations of NK cells exhibit immunological memory and contribute to the antitumour defence [76].…”

Molecular Profiling of Keratinocyte Skin Tumors Links Staphylococcus aureus Overabundance and Increased Human β-Defensin-2 Expression to Growth Promotion of Squamous Cell Carcinoma

“…Such an example was recently shown in colorectal carcinogenesis, wherein overexpression of a specific bacterial lectin (Gal-GalNAc) on the neoplastic colon epithelium leads to selective enrichment of tumor-driving Fusobacterium nucleatum [9]. Notably, bacteria can contribute to neoplastic processes in various ways, which include the production of genotoxins leading to DNA damage or their ability to influence the tumor microenvironment such as the immune system in the vicinity of the tumor [10,11]. Indeed, it was shown recently that in an animal model of keratinocyte skin cancer due to chronic inflammation, tumor formation was dependent on bacterial infection and was specifically driven by flagellin (the ligand for TLR-5), whereas antibiotic treatment inhibited tumor formation [12].…”

Cutaneous Squamous Cell Carcinoma: From Biology to Therapy

“…The signaling pathways involved in CSCC development have given rise to targetable molecules in recent decades. Moreover, the high mutational burden and increased risk of CSCC in patients under immunosuppression were part of the rationale for developing the immunotherapy for CSCC that has changed the therapeutic landscape in recent years [30]. This review focuses on the molecular basis of CSCC and the current biology-based approaches of targeted therapies and immune checkpoint inhibitors.…”