Loss of Skeletal Muscle Mass Is Associated With Reduced Cytotoxic T Cell Abundance and Poor Survival in Advanced Lung Cancer

ABSTRACT Background Body composition alterations such as skeletal muscle (SM) loss in cancer patients are associated with poor survival. In turn, immune cell‐driven pathways have been linked to muscle wasting. We aimed to investigate the relationship between body composition, tumour‐infiltrating lymphocytes and survival in patients with advanced lung cancer. Methods We studied 200 patients with advanced lung cancer receiving immunotherapy ( n = 81) or non‐immunotherapy regimens ( n = 119). Body composition including SM index (SMI) at baseline and longitudinal changes were assessed using computed tomography (CT) scans at the third lumbar vertebra. Associations between body composition parameters and overall survival (OS) were evaluated using Cox regression analysis. The median value of SMI, stratified by sex, was used as the cut‐off to define groups with high and low baseline SMI. Stable SMI was defined by any increase or < 2% decrease per 100 days; loss of SMI was defined by ≥ 2% decrease per 100 days. Logistic regression analysis was applied to investigate the association between SMI and peripheral circulating immune cells. Tumour‐infiltrating lymphocytes were identified by immunohistochemistry, and their relationship with SMI was evaluated. Results SMI loss was associated with shorter OS (whole cohort: HR = 2.314, 95% CI = 1.388–3.858, p = 0.001; immunotherapy cohort: HR = 3.028, 95% CI = 1.113–8.236, p = 0.03; non‐immunotherapy cohort: HR = 2.298, 95% CI = 1.191–4.435, p = 0.013). Low baseline SMI was associated with higher CD3 + T cell abundance (OR = 1.240, 95% CI = 1.080–1.424, p = 0.002) but lower CD3 + CD8 + T cell abundance (OR = 0.862, 95% CI = 0.762–0.974, p = 0.018) in peripheral blood. Subsequent SMI loss during treatment was also significantly associated with higher CD3 + T cell counts (OR = 3.414, 95% CI = 1.301–8.961, p = 0.013) and lower CD3 + CD8 + T cell abundance (OR = 0.666, 95% CI = 0.459–0.968, p = 0.033). Patients with stable SMI had a higher number of CD8 + tumour‐infiltrating lymphocytes than patients with SMI loss (15.4% vs. 7.9%, p = 0.036). Conclusion SM loss is an independent predictor for survival in patients with advanced lung cancer and is associated with reduced peripheral and tumour‐infiltrating cytotoxic T cell abundance. An inadequate antitumour immune response may contribute to metabolic tissue wasting in cancer.