Overcoming Resistance to Immunotherapy in Advanced Cutaneous Squamous Cell Carcinoma

Cutaneous squamous cell carcinoma (CSCC) is the second most frequent cancer in humans, and is now responsible for as many deaths as melanoma. Immunotherapy has changed the therapeutic landscape of advanced CSCC after the FDA approval of anti-PD1 molecules for the treatment of locally advanced and me...

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Bibliographic Details
Published in:Cancers 2021-10, Vol.13 (20), p.5134
Main Authors: García-Sancha, Natalia, Corchado-Cobos, Roberto, Bellido-Hernández, Lorena, Román-Curto, Concepción, Cardeñoso-Álvarez, Esther, Pérez-Losada, Jesús, Orfao, Alberto, Cañueto, Javier
Format: Article
Language:English
Subjects:
Antigens
Biomarkers
Cancer therapies
Chemotherapy
Clinical trials
Disease control
Disease resistance
FDA approval
Gene expression
Immune checkpoint inhibitors
Immune system
Immunogenicity
Immunomodulation
Immunotherapy
Lymphocytes
Medical prognosis
Melanoma
Metastases
Metastasis
Mutation
Oncolysis
Patients
PD-1 protein
Radiation therapy
Response rates
Review
Squamous cell carcinoma
Surgery
T cell receptors
Tumor microenvironment
Vaccines
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Summary:Cutaneous squamous cell carcinoma (CSCC) is the second most frequent cancer in humans, and is now responsible for as many deaths as melanoma. Immunotherapy has changed the therapeutic landscape of advanced CSCC after the FDA approval of anti-PD1 molecules for the treatment of locally advanced and metastatic CSCC. However, roughly 50% of patients will not respond to this systemic treatment and even those who do respond can develop resistance over time. The etiologies of primary and secondary resistance to immunotherapy involve changes in the neoplastic cells and the tumor microenvironment. Indirect modulation of immune system activation with new therapies, such as vaccines, oncolytic viruses, and new immunotherapeutic agents, and direct modulation of tumor immunogenicity using other systemic treatments or radiotherapy are now under evaluation in combined regimens. The identification of predictors of response is an important area of research. In this review, we focus on the features associated with the response to immunotherapy, and the evaluation of combination treatments and new molecules, a more thorough knowledge of which is likely to improve the survival of patients with advanced CSCC.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers13205134