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.

Source:

Mees D. Egeler, Sebastian Klobuch, Willemijn S. Tak, Maartje W. Rohaan, Troels H. Borch, Inge. M. Noringriis, Renaud Tissier, Minke W. Lucas, Winan van Houdt, Alexander C.J. van Akkooi, Inge Jedema, Marco Donia, Christian U. Blank, Inge Marie Svane, John B.A.G. Haanen, Lonneke V. van de Poll-Franse, The association between pretreatment emotional distress and response to tumor-infiltrating lymphocyte therapy in advanced melanoma, European Journal of Cancer, Volume 227, 2025, 115640, ISSN 0959-8049, https://doi.org/10.1016/j.ejca.2025.115640.

https://www.sciencedirect.com/science/article/abs/pii/S0959804925004228