Posted: Wednesday, December 7, 2022
Tricia Cottrell, MD, PhD, of Queen’s University, Kingston, Canada, and colleagues aimed to determine whether CD8-positive, FoxP3-positive cells are predictive of response to immunotherapy for resectable non–small cell lung carcinoma (NSCLC). During the 2022 Society for Immunotherapy of Cancer (SITC) Annual Meeting (Abstract 57), the investigators concluded that these cells associate with “major pathologic response and improved survival outcomes following neoadjuvant anti–PD-1 [therapy].”
“Based upon recent results in advanced melanoma showing that CD8-positive, FoxP3-positive cells were strongly associated with therapeutic response, we hypothesized that these cells would also be predictive of response in resectable NSCLC,” mentioned the investigators. “When detected by multiplex immunofluorescence in pretreatment NSCLC tumor specimens, these cells associate with major pathologic response and improved survival outcomes following neoadjuvant anti–PD-1 [therapy].”
Tumor specimens were obtained from the first-in-human clinical trial of neoadjuvant nivolumab (anti–PD-1) with or without ipilimumab (anti–CTLA-4) in NSCLC (ClinicalTrials.gov identifier NCT02259621). They were stained with a six-marker multiplex immunofluorescence panel to detect PD-1, PD-L1, CD8, CD163, FoxP3, and cytokeratin. Immune cell densities within the tumor microenvironment were analyzed to determine cell phenotypes and predict major pathologic response.
In patients who achieved a major pathologic response, the density of CD8-positive, FoxP3-positive cells appeared to be significantly elevated (P = .014; this correlation was the strongest among the PD-1–positive [P = .004] and PD-L1–negative [P = .007] subgroups). Of note, the AUC for CD8-positive, FoxP3-positive cells was stronger than for any other cell phenotype that was labeled using this multiplex immunofluorescence assay.
Compared with individuals whose tumor microenvironment lacked CD8-positive, FoxP3-positive cells (n = 7), those whose tumors harbored these cells had improved event-free survival (41 vs. 8 months; P = .041) and overall survival (26 vs. 8 months; P = .074). Of note, single-cell RNA-sequencing studies of the CD8-positive, FoxP3-positive T-cell subset demonstrated a transcriptome compatible with a highly activated, cytotoxic phenotype that highly expressed proteins CCL5, CD8A, GZMB, NKG7, CTSW, CD8B, LINC02446, and GZMK.
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