Cellular Senescence-Associated Gene Expression in Circulating CD4+, CD8+, CD19+ Lymphocytes of HNSCC Patients: Associations with Clinical Parameters

Senescence-associated secretory phenotype (SASP) signaling, along with key markers such as P16INK4a/CDKN2A and LMNB1, has not been systematically studied in circulating lymphocyte subsets in head and neck squamous cell carcinoma (HNSCC). This study aimed to evaluate SASP-related genes and senescence markers in peripheral CD4+, CD8+, and CD19+ cells and assess their clinical relevance. Expression of IL-6, IL-1β, TNFα, CXCL1, P16INK4a/CDKN2A, and LMNB1 was measured by RT-qPCR in sorted lymphocytes from 58 HNSCC patients at baseline, 31 post-treatment, and 13 controls. Statistical analyses included nonparametric tests, correlation analyses, and survival models (Kaplan–Meier, Cox regression). In the results, LMNB1 was significantly upregulated in all lymphocyte subsets of HNSCC patients. IL-6, CXCL1, and IL-1β were elevated in CD4+ T cells. A coordinated co-expression network involving IL-6, CXCL1, IL-1β, P16INK4a/CDKN2A, and LMNB1 was observed. Clinically, IL-6 in CD8+ T cells was associated with higher nodal stage and worse survival, while CXCL1 in CD19+ B cells independently predicted survival. No differences were found between pre- and post-treatment samples. Circulating lymphocytes in HNSCC display coordinated expression of selected senescence-associated genes, with IL-6 and CXCL1 as candidate prognostic biomarkers linked to tumor progression that warrant further validation.