The association between pretreatment emotional distress and response to tumor-infiltrating lymphocyte therapy in advanced melanoma

Aims: Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TILs) has demonstrated benefit for patients with advanced melanoma refractory to first-line immune checkpoint inhibitors (ICIs). However, predictive biomarkers for TIL therapy response are limited. Preclinical studies suggest that emotional distress (ED) may impair antitumor immune responses. We conducted a post-hoc analysis of the phase III TIL trial (NCT02278887) to evaluate the association between pretreatment ED and TIL therapy outcomes. Methods: ED was evaluated using a composite score derived from the Impact of Event Scale and the emotional functioning subscale of the EORTC QLQ-C15-PAL. Patients were stratified into elevated ED (n = 32) or normal ED (n = 40) groups using a median split approach. To evaluate whether the obtained results were dependent on the ED classification method, a sensitivity analysis was conducted to compare TIL therapy outcomes between patients with composite ED scores in the lowest tertile (normal ED, n = 26) and highest tertile (elevated ED, n = 25). Results: Elevated ED was associated with a reduced objective response rate (37 % vs. 69 %; adjusted odds ratio, 0.28; 95 % confidence interval [CI], 0.19–0.75; P = 0.013) and decreased progression-free survival rates at 1-year (31 % vs. 58 %) and 2-years (16 % vs. 35 %; adjusted hazard ratio, 1.84; 95 % CI, 1.03–3.26; P = 0.038). Sensitivity analysis using the tertile grouping method showed a similar trend (odds ratio, 0.35; 95 % CI, 0.11–1.08, P = 0.072). Conclusion: Our findings suggest that elevated ED before TIL therapy is associated with reduced therapeutic outcomes, underscoring the need for further investigation into the stress-immune-cancer axis.