Dados do Trabalho

Título

Association of monocarboxylate transporter family genes with immunotherapy outcomes in melanoma patients

Introdução

Several studies have shown the correlation between tumor metabolism, immune response, and disease progression. Glycolytic activity and lactate uptake lead to immune exhaustion in melanoma, but the associated pathways and their implications in clinical practice are yet to be elucidated.

Objetivo

This study aimed to investigate the prognostic potential of two genes from the solute carrier (SLC) 16 gene family, namely SLC16A11 and SLC16A13, in a cohort of melanoma patients treated with immune checkpoint blockade (ICB).

Métodos

FFPE tumor samples from 30 patients with advanced melanoma who underwent anti-PD-1 immunotherapy were collected. Patients exhibiting tumor progression were categorized as non-responders, while patients demonstrating partial and complete response or with stable disease for more than 6 months were classified as responders. The expression levels of SLC16A11 and SLC16A13 were analyzed using the NanoString nCounter methodology. The release of immune mediators into plasma was evaluated by Cytometric Bead Array. Statistical analyses were performed using SPSS 23.0 software. The study was approved by the Research Ethics Committee of Barretos Cancer Hospital (#1772/2019).

Resultados

Sixteen (53.3%) patients presented disease progression after ICB treatment. Lack of therapeutic response was associated with increased expression of both SLC16A11 and SLC16A13 genes (p=0.024 and p=0.011, respectively). Moreover, higher SLC16A11 expression was associated with higher IL-4 plasmatic concentration (r=0.363; p=0.048) and inversely correlated with PD-L1 primary tumor expression (r=-0.371; p=0.044). Finally, elevated expression of these two genes led to reduced overall survival following immunotherapy treatment (p=0.017 and p=0.003, respectively).

Conclusões

SLC16A11 and SLC16A13 emerged as predictive markers of poor response and lower overall survival in advanced melanoma patients undergoing anti-PD-1 therapies. Future prospective studies are crucial to validate their clinical potential in a broader setting.

Palavras-chave

Melanoma; Immune checkpoint inhibitors; Predictive markers

Financiador do resumo

This research was funded by the São Paulo Research Foundation (FAPESP, #2019/07111-9) and the Researchers Assistance and Incentive Program (PAIP - Barretos Cancer Hospital). Sorroche, BP was a recipient of scholarships from FAPESP (#2019/03570-9 and #2021/10922-9). Arantes, LMRB was a recipient of the National Council for Scientific and Technological Development (CNPq) productivity.