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Soo Park, MD
Soo Park, MD
Posted: Wednesday, August 21, 2024
According to a study published in Nature Communications, the increased number of patients with cutaneous squamous cell carcinoma (SCC) who remain unresponsive to immune checkpoint blockade therapy or develop resistance to such treatment has influenced current investigative efforts to focus on identifying effective therapeutic strategies. Laura Lorenzo-Sanz, PhD, of L’Hospitalet de Llobregat, Barcelona, and colleagues suggest incorporating the epithelial and mesenchymal features of cancer cells when selecting the optimal immune checkpoint blockade treatment in this patient population.
“Overall, our findings reveal that personalized immune checkpoint blockade therapies should be selected on the basis of cancer cell features,” the investigators summarized.
Tissue samples from patients with locally advanced and metastatic cutaneous SCC, stage III and IV head and neck SCC, and stage IIIC melanoma were analyzed in the present study. Samples from the cutaneous SCC and head and neck SCC cohorts were stratified based on their response to anti–PD-1 or PD-L1 treatment. Samples from the melanoma cohort were stratified based on relapse after anti–PD-1 therapy. In addition, cutaneous SCC cells were obtained from mouse models and subjected to multiple cellular assays.
The study authors reported an acquired plasticity in epithelial and mesenchymal cells during progression of cutaneous SCC. Alterations in the immune checkpoint ligand profile were also noted during the progression of this cancer. Antitumor immune responses were differentially blocked by the PD-1/PD-L1 pathway in epithelial cancer cells and the cytotoxic T-lymphocyte-associated protein 4/CD80 and TIGIT/CD155 pathways in mesenchymal cancer cells. Furthermore, these pathways assist in determining the response to immune checkpoint blocker therapies, they noted. Moreover, if the cutaneous SCC contains both epithelial and mesenchymal cancer cells, the most effective therapeutic approach should target a combined anti–PD-L1/TIGIT pathway., Dr. Lorenzo-Sanz and colleagues proposed.
Disclosure: Dr. Lorenzo-Sanz reported no conflicts of interests. For full disclosures of the other study authors, visit nature.com.
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