Cutaneous Squamous Cell Carcinoma in the Age of Immunotherapy

Cutaneous squamous cell carcinoma (cSCC) is the second most prevalent skin cancer globally. Because most cSCC cases are manageable by local excision/radiotherapy and hardly become life-threatening, they are often excluded from cancer registries in most countries. Compared with cutaneous melanoma that originates from the melanin-producing, neural crest-derived epidermal resident, keratinocyte (KC)-derived cancers are influenced by the immune system with regards to their pathogenetic behaviour. Congenital or acquired immunosurveillance impairments compromise tumoricidal activity and raises cSCC incidence rates. Intriguingly, expanded applications of programmed death-1 (PD-1) blockade therapies have revealed cSCC to be one of the most amenable targets, particularly when compared with the mucosal counterparts arisen in the esophagus or the cervix. The clinical observation reminds us that cutaneous tissue has a peculiarly high immunogenicity that can evoke tumoricidal recall responses topically. Here we attempt to redefine cSCC biology and review current knowledge about cSCC from multiple viewpoints that involve epidemiology, clinicopathology, molecular genetics, molecular immunology, and developmental biology. This synthesis not only underscores the primal importance of the immune system, rather than just a mere accumulation of ultraviolet-induced mutations but also reinforces the following hypothesis: PD-1 blockade effectively restores the immunity specially allowed to exist within the fully cornified squamous epithelium, that is, the epidermis.

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Investigating epidemiologic trends and the geographic distribution of patients with anal squamous cell carcinoma throughout Canada

Current Oncology ◽

10.3747/co.27.6061 ◽

2020 ◽

Vol 27 (3) ◽

Author(s):

L. Cattelan ◽

F. M. Ghazawi ◽

M. Le ◽

E. Savin ◽

A. Zubarev ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Anal Cancer ◽

Squamous Cell ◽

Demographic Data ◽

Cancer Registries ◽

The United States ◽

Incidence Rates ◽

Anal Squamous Cell Carcinoma ◽

Incidence And Mortality

Background Anal cancer is a rare disease, constituting 0.5% of new cancer cases in the United States. The most common subtype is squamous cell carcinoma (scc). Studies in several developed nations have reported on an increasing incidence of anal cancer in recent decades, and various risk factors pertaining to the pathogenesis of the disease have been identified, including infection with the human papillomavirus, tobacco use, and immunosuppression. The epidemiology and distribution of anal scc throughout Canada remain poorly understood, however. Methods Using 3 population-based cancer registries, a retrospective analysis of demographic data across Canada for 1992–2010 was performed. The incidence and mortality for anal scc was examined at the levels of provinces, cities, and the forward sortation area (FSA) component (first 3 characters) of postal codes. Results During 1992–2010, 3720 individuals were diagnosed with anal scc in Canada; 64% were women. The overall national incidence rate was 6.3 cases per million population per year, with an average age at diagnosis of 60.4 years. The incidence increased over time, with significantly higher incidence rates documented in British Columbia and Nova Scotia (9.3 cases per million population each). Closer examination revealed clustering of cases in various urban centres and self-identified lgbtq communities in Toronto, Montreal, and Vancouver. Discussion This study provides, for the first time, a comprehensive analysis of the burden of anal scc in Canada, identifying susceptible populations and shedding light onto novel avenues of research to lower the incidence of anal cancer throughout the country.

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The Role of the Immune System in Cutaneous Squamous Cell Carcinoma

International Journal of Molecular Sciences ◽

10.3390/ijms20082009 ◽

2019 ◽

Vol 20 (8) ◽

pp. 2009 ◽

Cited By ~ 19

Author(s):

Matthew J. Bottomley ◽

Jason Thomson ◽

Catherine Harwood ◽

Irene Leigh

Keyword(s):

Squamous Cell Carcinoma ◽

Immune System ◽

Cell Carcinoma ◽

Squamous Cell ◽

Ex Vivo ◽

Metastatic Potential ◽

Cutaneous Squamous Cell Carcinoma ◽

Lessons Learned ◽

Considerable Morbidity

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.

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