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Soo Park, MD
Soo Park, MD
Posted: Friday, August 16, 2024
According to researchers, immune checkpoint blockade therapy elicits response in only about 50% of cases of Merkel cell carcinoma. To evaluate potential mechanisms of resistance to such treatment, Kenneth Tsai, MD, PhD, of Moffitt Cancer Center, Tampa, Florida; Jaehyuk Choi, MD, PhD, of Northwestern University, Chicago; and colleagues reportedly conducted the largest multimodal analysis of the tumor microenvironment among patients with Merkel cell carcinoma. The results of this study were published in the journal Cancer Discovery.
“Our findings not only highlight the potential to use specific genes and immune cells as biomarkers for predicting patient response to immune checkpoint blockade therapy, but also suggest several approaches for abrogating resistance and enhancing efficacy,” stated Dr. Tsai in a Moffitt press release. “Importantly, patients with tumors already containing the right mix of immune cells before treatment were more likely to respond, suggesting that increasing their numbers with the correct localization could enhance treatment outcomes.”
A total of 186 samples from 116 patients with Merkel cell carcinoma were obtained. Bulk RNA sequencing, single-cell RNA sequencing, multiplexed immunofluorescence, and spatial transcriptomics were performed on samples from 71, 64, 41, and 20 patients, respectively; bulk RNA sequencing from 14 matched pairs was done before and after immune checkpoint blockade.
Tumor proliferation, the presence of interleukin-1, and neuronal stem cell markers were discovered in samples of patients who did not respond to immunotherapy. Of note, those who responded to immune checkpoint inhibitors had preexisting tissue-resident CD8 or Vδ1 gamma-delta T cells and increased type I/II interferons, which interact with the clonal expansion of public T-cell receptors and antigen-specific induction of antitumor cytokines and cytotoxic enzymes.
Co-localization of B cells and dendritic cells and T cells were identified via spatial transcriptomics. Furthermore, immune checkpoint blockade therapy was found to significantly increase the recruitment or clonal expansion of tissue-resident memory T cells and Vδ1 cells among responders.
Disclosure: For full disclosures of the study authors, visit aacrjournals.org.
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