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Karl D. Lewis, MD


Immunotherapy for Skin Cancer: Predicting Who Is Likely to Benefit Most

By: Celeste L. Dixon
Posted: Thursday, August 25, 2022

Predicting which patients with advanced and metastatic non-melanoma skin cancer might be likely to benefit most from immunotherapy is the focus of current research. At present, not only are the treatments costly, but so are the ways to attempt to identify such patients, wrote Iris Zalaudek, MD, of the University of Trieste, Italy, and colleagues, in the Journal of Clinical Medicine.

The authors concluded that “definitive, cost-effective, and reproducible biomarkers are still lacking, and further efforts are needed to validate the suggested predictors in larger cohorts.” Properly identifying patients as suitable—or unsuitable—immunotherapy candidates is especially important because immunotherapeutic agents are already known not to be effective in all patients and may lead to severe adverse effects in some. Based on emerging evidence, the study authors noted, elderly individuals and those with autoimmune conditions generally might benefit from immunotherapy; this was less true of organ transplantation recipients.

In patients with cutaneous squamous cell carcinoma, higher tumor mutation burden, genetic alterations in the 3q chromosomal arm, and PD-L1–positive status all tended to be associated with positive clinical responses, the investigators wrote. In Merkel cell carcinoma, they noted, Merkel cell polyomavirus status and PD-L1–positive expression (≥ 1%) were not useful predictors of response, but PD-1 and PD-L1 density, PD-L1/PD-1 proximity, and features of tumor-infiltrating lymphocytes’ T-cell receptor repertoire (with low clonality and high diversity) tended to be associated with good outcomes. “Supportive data for basal cell carcinoma are…scarce, probably because immunotherapy use is less common for this tumor,” they also noted.

Dr. Zalaudek and co-investigators stressed that currently, “many of these proposed biomarkers are assessed by employing complex, expensive, and not easily reproducible genetic, immunohistochemistry, or immunofluorescence techniques. [They] are potentially difficult to use in daily practice and not cost-effective.” Potentially, “a more simple and reproducible approach is represented by serum biomarkers, such as absolute lymphocyte count, but their role should be confirmed by further studies.”

Disclosure: The study authors reported no conflicts of interest.

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