A RECENT study explored the impact of pretreatment emotional distress (ED) on the outcomes of tumour-infiltrating lymphocyte (TIL) therapy in patients with advanced melanoma. TIL therapy is a form of adoptive cell therapy (ACT) that has shown promise for patients who do not respond to first-line immune checkpoint inhibitors.
However, there remains a lack of reliable predictive biomarkers to determine which patients will benefit most from TIL therapy. Given preclinical evidence suggesting that emotional distress can impair antitumour immune responses, the researchers analysed data from the Phase III TIL trial (NCT02278887) to examine whether elevated levels of ED before treatment affected therapy success.
Emotional distress was assessed using a composite score derived from two validated tools: the Impact of Event Scale and the emotional functioning subscale of the EORTC QLQ-C15-PAL questionnaire. Patients were divided into groups based on their distress levels, with 32 patients classified as having elevated ED and 40 patients with normal ED using a median split. The researchers also conducted a sensitivity analysis comparing the highest and lowest thirds of distress scores to confirm the robustness of their findings.
Results demonstrated a clear association between elevated ED and poorer TIL therapy outcomes. Patients with higher distress exhibited a significantly lower objective response rate to the therapy (37% versus 69%), with an adjusted odds ratio of 0.28, indicating they were less likely to respond favourably. Additionally, elevated ED correlated with shorter progression-free survival, with fewer patients free from disease progression at both one and two years post-treatment. The sensitivity analysis supported these trends, although with slightly less statistical significance.
These findings suggest that pretreatment emotional distress may be a modifiable host factor influencing the effectiveness of immunotherapy in melanoma. They highlight the importance of further research into the interplay between psychological stress, immune function, and cancer progression, and suggest that addressing ED could enhance treatment outcomes for patients undergoing TIL therapy.
Reference
Egeler MD et al. The association between pretreatment emotional distress and response to tumor-infiltrating lymphocyte therapy in advanced melanoma. Eur J Cancer. 2025;DOI:10.1016/j.ejca.2025.115640
