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Novel T-Cell Therapy After PD-1 Blockade Under Study in Merkel Cell Carcinoma

By: Joshua D. Madera, MD
Posted: Wednesday, March 20, 2024

For patients with Merkel cell carcinoma who were treated with PD-L1 blockade, innate-like T cells may play a contributory role in the antitumor response, according to a study published in Nature Communications. These findings may guide future investigative efforts to develop novel cancer immunotherapies that will augment this response, suggested Pamela S. Ohashi, PhD, FRSC, of the Princess Margaret Cancer Centre, Toronto, Canada, and colleagues.

A total of six patients with Merkel cell carcinoma were recruited for the INSPIRE study. All were treated with the PD-L1 inhibitor pembrolizumab for a maximum of 2 years. Tumors were biopsied at baseline and during treatment at either week 6 or week 9. Tissue samples were subjected to flow cytometry analysis and T-cell receptor sequencing. In addition, peripheral blood samples were obtained from patients at baseline and during treatment at weeks 3, 6, 9, and 15. After the sample was obtained at week 15, routine peripheral blood samples were continuously obtained at 9-week intervals and at the end of treatment.

The study authors reported that after treatment with pembrolizumab, a complete response was observed in one patient, partial responses were observed in two patients, and disease progression was observed in three patients. Flow cytometry revealed a large expansion in the frequency of γδ T cells in both the tumor and blood in the patient who demonstrated a complete response to treatment. The increase in γδ T cells was more substantial in the tumor biopsy sample. Moreover, the intratumoral γδ T cells demonstrated an increased expression of PD-L1 and TIGIT (T-cell immunoreceptor with immunoglobulin and ITIM domain) compared with CD4 and CD8 expression. Furthermore, comparing the T-cell receptor expression between the tumor and blood in the patient who demonstrated a complete response to treatment revealed a comparable TRD repertoire.

Disclosure: For full disclosures of the study authors, visit

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