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Gregory J. Riely, MD, PhD
Gregory J. Riely, MD, PhD
Posted: Wednesday, March 27, 2024
FLT3, a receptor tyrosine kinase expressed by immature hematopoietic cells, may prove to be a future target for tumor immunotherapy. Signaling through the FLT3 receptor facilitates the generation of mature natural killer (NK) cells and dendritic cells (DCs) and is required for T-cell activation. Lukasz Kuncman, MD, PhD, of the Medical University of Lodz, Poland, and colleagues investigated the prevalence of FLT3 in the tumor microenvironment of two common types of non–small cell lung cancer: adenocarcinoma and squamous cell carcinoma. Their research, recently published in the journal Molecular Oncology, suggested that FLT3 expression may be a useful prognostic factor for disease-free survival in patients with this type of lung cancer.
“High expression of FLT3 in the tumor microenvironment was associated with immune cell infiltration (especially of NK cells and DCs), increased expression of T-cell exhaustion markers, and expression of effector genes of the cGAS-STING pathway, which may consequently increase susceptibility to immunotherapy and radiotherapy,” the investigators noted.
The researchers gathered genomic data from 515 patients (median age, 66 years) with adenocarcinoma and 501 patients (median age, 68 years) with squamous cell carcinoma from The Cancer Genome Atlas Database. FLT3 gene-expression data, as well as disease-free survival data, were extracted for 422 of the 515 patients in the adenocarcinoma cohort and 392 of the 501 patients in the squamous cell carcinoma cohort.
Disease-free survival differed between the FLT3-low and FLT3-high groups, respectively, for both the squamous cell cohort (61.0 vs 71.3 months; hazard ratio [HR] = 0.61, 95% confidence interval [CI] = 0.35–1.06, P = .075) and the adenocarcinoma cohort (32.7 vs 47.5 months; HR = 0.69, 95% CI = 047–0.99, P = .045). In both cohorts, patients whose tumor microenvironments featured FLT3-high expression had higher infiltration of all immune cells assessed (including but not limited to T cells, NK cells, DCs, B cells, monocytes, macrophages, and tumor-associated fibroblasts).
Disclosure: For full disclosures of the study authors, visit febs.onlinelibrary.wiley.com.
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