Understanding the squamous cell carcinoma immune microenvironment

Abstract

Primary cutaneous squamous cell carcinoma (cSCC) is the second most common human cancer with a rising incidence of about 1.8 million in the United States annually. Primary cSCC is usually curable by surgery; however, in some cases, cSCC eventuates in nodal metastasis and death from disease specific death. cSCC results in up to 15,000 deaths each year in the United States. Until recently, non-surgical options for treatment of locally advanced or metastatic cSCC were largely ineffective. With the advent of checkpoint inhibitor immunotherapy, including cemiplimab and pembrolizumab, response rates climbed to 50%, representing a vast improvement over chemotherapeutic agents used previously. Herein, we discuss the phenotype and function of SCC associated Langerhans cells, dendritic cells, macrophages, myeloid derived suppressor cells and T cells as well as SCC-associated lymphatics and blood vessels. Possible role(s) of SCC-associated cytokines in progression and invasion are reviewed. We also discuss the SCC immune microenvironment in the context of currently available and pipeline therapeutics.

Ex vivo therapeutic screening of metastatic cSCC: A review of methodological considerations for clinical implementation

“…First, these cell lines lack the structural, in vivo complexity of metastatic cSCC 15,37 . Even UW‐CSCC spheroids lack complex cell‐stromal interactions, TME, distinctive cancer‐associated cell populations and other complex interactions that mediate therapeutic response as extensively described elsewhere 14,38–41 . It is largely this disconnect between in vitro and in vivo tumour behaviour that underscores the poor translation of therapeutics that appear promising in cell line models but lack efficacy in more complex, in vivo models and indeed in the clinical setting.…”

“…15,37 Even UW-CSCC spheroids lack complex cellstromal interactions, TME, distinctive cancer-associated cell populations and other complex interactions that mediate therapeutic response as extensively described elsewhere. 14,[38][39][40][41] It is largely this disconnect between in vitro and in vivo tumour behaviour that underscores the poor translation of therapeutics that appear promising in cell line models but lack efficacy in more complex, in vivo models and indeed in the clinical setting. For example, UW-CSCC1 was demonstrated to downregulate expression of many cancer pathways compared to both the patient tumour from which it was derived and cell line xenograft models.…”

Combined analysis of bulk and single-cell RNA sequencing reveals novel natural killer cell-related prognostic biomarkers for predicting immunotherapeutic response in hepatocellular carcinoma

“…Additionally, the interaction between immune cells and tumor cells in the TME not only influences a patient’s prognosis but may also alter a patient’s response to immunotherapy ( 2 ). The importance of innate immune cells has not gotten enough attention in the contemporary setting of antitumor immunity, which has mostly focused on adaptive T-cell responses, like CD4+ CD25+ Foxp3 regulatory T cells (Tregs), cytotoxic T lymphocytes (CTLs) et all ( 3 , 4 ). By specifically identifying and eliminating tumor cells and encouraging adaptive T-cell immunity responses, natural killer (NK) cells are a subtype of innate immune cells that can reduce the proliferative and invasive potential of tumor cells at an early tumor stage ( 5 ).…”

Recent Advances in Clinical Research for Skin Cancer Chemoprevention

“…However, some lesions can be highly destructive if left untreated. SCC is the second most prevalent type of skin cancer, with an estimated annual occurrence of 1.8 million cases within the United States [6]. SCC is an uncontrolled and abnormal growth of squamous cells that are in the epidermis layer (Figure 1).…”

“…Like BCC, SCC is also found in similar places exposed to the sun, such as the face, ears, scalp, neck, and hands. SCCs share similar risk factors to BCC but with the addition of a weakened SCC is the second most prevalent type of skin cancer, with an estimated annual occurrence of 1.8 million cases within the United States [6]. SCC is an uncontrolled and abnormal growth of squamous cells that are in the epidermis layer (Figure 1).…”