Adaptive immune signatures in tumor biopsy samples obtained early during the course of treatment may be used to predict patient response to melanoma immunotherapy, according to a study published in Cancer Discovery.
Immune checkpoint inhibitors have emerged as a major breakthrough in cancer therapy, but how well patients respond to treatment can vary significantly. Certain genomic and immune features in pretreatment tumor biopsies have been reported to correlate with response in patients with melanoma and other cancer types; however, a robust set of biomarkers has not yet been established.
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Therefore, researchers led by Jennifer A Wargo, The University of Texas MD Anderson Cancer Center (Houston, TX), assembled a cohort of longitudinal tumor samples from patients with melanoma and analyzed each biopsy for gene expression and the presence of certain types of T cell and protein markers, such as the expression of programmed cell death protein (PD-1) and programmed death ligand 1.
Patients included in the study were first treated with cytotoxic T-lymphocyte associated antigen 4 inhibitor ipilimumab. Biopsies then followed after the second or third line of treatment and at progression. Overall, 7 of 53 eligible patients had clinical benefit. The remaining 46 patients proceeded to treatment with the PD-1 inhibitor pembroluzimab, to which 13 patients (28%) responded.
When they compared the immune profiles of responders and non-responders, researchers found that there were significant differences in nearly all of the 12 immune markers after anti-PD-1 treatment, including density in the tumor of killer cluster of differentiation 8 T cells, cluster of differentiation 4 helper T cells, and cluster of differentiation 3 T cells that also assist killer cells, as well as the presence of PD-1, PD-L1, and the immune checkpoint molecule lymphocyte-activation gene 3.
Additionally, in responders, researchers observed differences in more than 400 different gene types, mostly those involved in immune response. Only six genes had a lower expression in responders, including vascular endothelial growth factor (VEGFA), which helps to regulate angiogenesis. These data suggest that VEGFA could be a potential target for cancers that have become resistant to treatment, a finding that is consistent with prior research.
Researchers concluded that adaptive immune signatures in early on-treatment tumor biopsies are predictive of response to checkpoint blockade and provide insight on different mechanism associated with therapeutic response, which could help to inform treatment decisions and guide future therapeutic research. These findings also highlight the importance of obtaining biopsy samples during early treatment.
“Before treatment, analyzing samples with a 12-marker immune panel or a 795-gene expression panel, you can’t tell who will respond with any degree of certainty,” said Dr Wargo in a press statement. “On treatment, there were night-and-day differences between responders and non-responders.”
