A new study published in Cancer Discovery suggests that Merkel cell carcinoma patients with higher levels of preexisting tissue-resident CD8 T cells or Vδ1 γδ T cells within their tumours respond better to immune checkpoint blockade therapy.
In collaboration with scientists at Robert H. Lurie Comprehensive Cancer Center of Northwestern University in Illinois, researchers from the Moffitt Cancer Center in Florida analyzed samples from 116 Merkel cell carcinoma patients to gain insights into the immune response and tumour characteristics. Their findings showed that specific immune cells, particularly tissue resident CD8 T cells and γδ T cells, play a crucial role in the body’s response to immune checkpoint blockade therapy.
The research team, co-led by Kenneth Tsai, MD, PhD, vice chair of Pathology Research at Moffitt, and Jaehyuk Choi, MD, PhD, at Northwestern University, discovered that those who respond to immune checkpoint blockade therapy have higher levels of preexisting tissue-resident CD8 T cells or Vδ1 γδ T cells within their tumours.
According to a press release from Moffitt, these cells exhibit unique transcriptional programs and clonal expansion reflective of antigen specificity. This allows the cells to recognize and attack cancer cells effectively. In contrast, tumours from those who do not respond to immunotherapy showed increased proliferation and markers associated with neuronal stem cells, as well as the inflammatory molecule interleukin (IL)-1.
The researchers demonstrated that these beneficial T cells are often found near other immune cells, such as B cells and dendritic cells. These help to enhance their activity by supplying necessary chemokines and costimulation. This close cellular interaction within the tumour microenvironment is a key factor in the effectiveness of the immune response.
“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,” Dr. Tsai said in the release.
“Importantly, patients with tumours 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.”
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