Immune mechanisms and predictive biomarkers related to neoadjuvant immunotherapy response in stage III melanoma
Amanda Braga Figueiredo,
Milton José Barros e Silva,
Guilherme Ferreira de Britto Evangelista,
Nayane Alves de Lima Galdino,
Larissa de Melo Kuil,
Iasmim Polido Santos,
Kátia Luciano Pereira Morais,
Clara Maciel Cavalcanti,
Luciana Facure Moredo,
João Pedreira Duprat-Neto,
Kenneth J Gollob
Affiliations
Amanda Braga Figueiredo
Translational Immuno-Oncology Group, International Research Center, A.C. Camargo Cancer Center, São Paulo, SP, Brazil; Translational Immuno-Oncology Laboratory, Education and Research Center, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil; Center for Research in Immuno-Oncology (CRIO), Hospital Israelita Albert Einstein, São Paulo, SP, Brazil
Milton José Barros e Silva
Clinical Oncology Department, AC Camargo Cancer Center, São Paulo, Brazil
Guilherme Ferreira de Britto Evangelista
Translational Immuno-Oncology Group, International Research Center, A.C. Camargo Cancer Center, São Paulo, SP, Brazil
Nayane Alves de Lima Galdino
Translational Immuno-Oncology Group, International Research Center, A.C. Camargo Cancer Center, São Paulo, SP, Brazil
Larissa de Melo Kuil
Translational Immuno-Oncology Group, International Research Center, A.C. Camargo Cancer Center, São Paulo, SP, Brazil
Iasmim Polido Santos
Translational Immuno-Oncology Group, International Research Center, A.C. Camargo Cancer Center, São Paulo, SP, Brazil
Kátia Luciano Pereira Morais
Translational Immuno-Oncology Group, International Research Center, A.C. Camargo Cancer Center, São Paulo, SP, Brazil
Clara Maciel Cavalcanti
Translational Immuno-Oncology Group, International Research Center, A.C. Camargo Cancer Center, São Paulo, SP, Brazil
Luciana Facure Moredo
Cutaneous Oncology Department, AC Camargo Cancer Center, São Paulo, Brazil
João Pedreira Duprat-Neto
Cutaneous Oncology Department, AC Camargo Cancer Center, São Paulo, Brazil
Kenneth J Gollob
Translational Immuno-Oncology Group, International Research Center, A.C. Camargo Cancer Center, São Paulo, SP, Brazil; Translational Immuno-Oncology Laboratory, Education and Research Center, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil; Center for Research in Immuno-Oncology (CRIO), Hospital Israelita Albert Einstein, São Paulo, SP, Brazil; Corresponding author. Centro de Ensino e Pesquisa – Hospital Israelita Albert Einstein, Rua Comendador Elias Jafet, 755, Morumbi, Sao Paulo, SP, 05653-010, Brazil.
The treatment for stage III melanoma has advanced significantly, nevertheless, a substantial proportion of patients experience relapse. Neoadjuvant immune checkpoint blockade has emerged as a promising approach, allowing early micrometastatic disease treatment, reduction of tumor burden before surgery, and enhanced tumor-specific T-cell responses. However, not all patients respond to treatment, highlighting the need for understanding immune mechanisms behind failure and identification of predictive markers. Here we performed a robust evaluation of systemic and tumoral immune profiles in a well-defined cohort of advanced melanoma patients treated with immune checkpoint inhibitors. Elevated CTACK and CXCL9 chemokines pre-treatment suggested their potential as predictive tools for treatment response. Furthermore, CD95 expression in CD8+ T lymphocytes surfaced as a favorable prognostic indicator, while PD-1, CD161, and PD-L2 exhibited correlations with worst outcomes. These findings shed light on the intricate interplay between immune markers and melanoma response to neoadjuvant immune checkpoint therapy, offering insights into personalized treatment strategies.
