Association of T Cell Senescence with Radiation Pneumonitis in Patients with Non-small Cell Lung Cancer

• Published in: International journal of radiation oncology, biology, physics Vol. 115; no. 2; pp. 464 - 475
• Main Authors: Kim, Kyung Hwan, Pyo, Hongryull, Lee, Hoyoung, Oh, Dongryul, Noh, Jae Myoung, Ahn, Yong Chan, Kim, Chang Gon, Yoon, Hong In, Lee, Jiyun, Park, Sehhoon, Jung, Hyun-Ae, Sun, Jong-Mu, Lee, Se-Hoon, Ahn, Jin Seok, Park, Keunchil, Ku, Bo mi, Shin, Eui-Cheol, Ahn, Myung-Ju
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2023
• Subjects: Carcinoma, Non-Small-Cell Lung; CD28 Antigens; CD8-Positive T-Lymphocytes; chemoradiotherapy; Humans; Lung Neoplasms; non-small cell lung cancer; peripheral blood; radiation pneumonitis; Radiation Pneumonitis - etiology; T cell senescence; T-Cell Exhaustion; non-small cell lung cancer; T cell senescence; chemoradiotherapy; peripheral blood; radiation pneumonitis
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/j.ijrobp.2022.07.018

Associations between immunosenescence and radiation pneumonitis (RP) are largely unknown. We aimed to identify a peripheral blood T cell senescence biomarker to predict RP in patients with non-small cell lung cancer (NSCLC). Patients with locally advanced NSCLC who received definitive concurrent chemoradiotherapy (dCRT) were prospectively registered (cohort 1, n=23; cohort 2, n=31). Peripheral blood was collected at baseline, during dCRT, and at 1 month post-dCRT. Patients were dichotomized to grade ≥2 (G2+) RP and grade 0-1 (G0-1) RP. Flow cytometry was performed to assess phenotypes and functional properties of T cell subsets. RP incidence was estimated via competing risk analysis. Five and six patients exhibited G2+ RP following dCRT in cohorts 1 and 2, respectively. Patients with G2+ RP exhibited a more aged T cell pool and higher frequencies of senescent CD57+CD28−CD8+ T cells than patients with G0-1 RP at baseline, during dCRT, and at 1 month post-dCRT. These senescent cells exhibited increased granzyme B, IFN-γ, and TNF-α production. Higher baseline frequency of CD57+CD28−CD8+ T cells was an independent predictor of G2+ RP (hazard ratio, 8.42; 95% confidence interval, 2.58–27.45; P<0.001). Recursive partitioning analysis revealed three distinct risk groups stratified by baseline CD57+CD28−CD8+ T cell frequency and lung V20 Gy, with 1-year cumulative G2+ RP incidences of 50.0%, 16.7%, and 0% for high-, intermediate-, and low-risk groups, respectively (P=0.002). Higher baseline frequencies of CD57+CD28−CD8+ T cells correlated with increased G2+ RP risks. Our results suggest the need for further investigation of the role of T cell senescence on radiation-induced organ damage.