Dr Kulasinghe on a Study Profiling the NSCLC Tumor Microenvironment

Arutha Kulasinghe, PhD, senior research fellow, Frazer Institute, the University of Queensland, discusses findings from a study profiling the tumor microenvironment of non–small cell lung cancer (NSCLC), which he presented during the 2023 IASLC World Conference on Lung Cancer, as well as future directions planned with this research and the implications of these findings.

The study included samples from 90 patients with NSCLC, 45 each of whom received an immune checkpoint inhibitor in the second line and standard-of-care platinum-based chemotherapy. Of the patients in the immunotherapy cohort, 16 responded with immunotherapy and 25 did not respond.

Investigators found that the enrichment of certain neighborhoods within the tumor tissue and tumor microenvironment was associated with varying responses to immunotherapy, Kulasinghe says. For instance, increased glucose uptake was present in tumors that experienced poor responses with immunotherapy, Kulasinghe explains. Other neighborhoods enriched in patients who did not respond to immunotherapy included regulatory T-cell monocytes, CD8-positive regulatory T cells, CD8-positive B cells, regulatory T-cell proliferating lymphocytes, and CD4-positive granulocytes. Neighborhoods enriched in patients who responded to immunotherapy included HLADR tumor macrophages, CD44-positive tumor mast cells, mixed tumor macrophages, mixed tumor effector CD4 cells, mixed tumor blood vessels, and CD8-positive HLADR tumor cells.

Efforts to measure these findings across multiple cohort studies are ongoing. Kulasinghe and his fellow study investigators are currently conducting retrospective analyses of previously published data on cohorts of patients who responded to immunotherapy vs those who did not respond in order to validate these findings across a larger dataset, Kulasinghe notes. So far, this research has included involved many single-site studies. Going forward, researchers aim to compare the findings from those studies with the findings from diverse patient populations in the United States and Europe. This research could help to determine the robustness and generalizability of the tissue signatures identified in this study, Kulasinghe concludes.