Introduction: Recent studies show that the gut microbiome topography score (Toposcore), a quantitative measure of microbial community organization, is associated with checkpoint inhibitor response and survival in melanoma. This study evaluates its association with outcomes in metastatic melanoma patients treated with TIL therapy.

Methods: We performed a retrospective analysis of 18 patients with metastatic melanoma who received TIL therapy and provided stool samples at predefined timepoints. The pre-TIL timepoint had the highest sample availability, with stool from 12 patients analyzed and assigned a Toposcore. Based on microbial composition, patients were categorized into three gut community signatures: SIG1 (dysbiotic), SIG2 (eubiotic), and a gray zone intermediate group. Pearson correlation coefficients and p values were calculated to assess associations between Toposcore and both progression-free survival (PFS) and overall survival (OS). Kaplan-Meier analysis compared PFS between microbial signature groups.

Results: Higher Toposcores demonstrated moderate positive correlations with both PFS (r = 0.47, p = 0.12) and OS (r = 0.50, p = 0.10). Kaplan–Meier analysis revealed significantly longer PFS in patients with Gray/SIG2 microbial signatures compared to those with SIG1 (p = 0.00028). Although correlation analyses did not reach statistical significance, these trends collectively suggest that a more eubiotic microbiome, reflected by higher Toposcore and Gray/SIG2 classification, is associated with improved clinical outcomes.

Conclusions: Toposcore and microbial signature classification were positively associated with PFS and OS in patients with metastatic melanoma treated with TIL therapy. These findings support emerging evidence that gut microbiome ecology influences antitumor immunity. Larger studies are warranted to validate Toposcore and microbial signatures as predictive biomarkers and to elucidate their mechanistic role in melanoma immunotherapy.