Attenuated mutants of Salmonella enterica Typhimurium mediate melanoma regression via an immune response

Autor(es)

Jorge, Genesy Perez ; Gontijo, Marco ; Floro e Silva, Marina ; Goes, Isabella Carolina Rodrigues Dos Santos ; Jaimes-Florez, Yessica Paola ; Coser, Lilian de Oliveira ; Rocha, Francisca Janaina Soares ; Giorgio, Selma ; Brocchi, Marcelo

• Tipo de documento: Artigo Científico
• Fonte: Experimental Biology and Medicine; v. 249, p. 19-pg., 2024-06-21.

Resumo

The lack of effective treatment options for an increasing number of cancer cases highlights the need for new anticancer therapeutic strategies. Immunotherapy mediated by Salmonella enterica Typhimurium is a promising anticancer treatment. Candidate strains for anticancer therapy must be attenuated while retaining their antitumor activity. Here, we investigated the attenuation and antitumor efficacy of two S. enterica Typhimurium mutants, Delta tolRA and Delta ihfABpmi, in a murine melanoma model. Results showed high attenuation of Delta tolRA in the Galleria mellonella model, and invasion and survival in tumor cells. However, it showed weak antitumor effects in vitro and in vivo. Contrastingly, lower attenuation of the attenuated Delta ihfABpmi strain resulted in regression of tumor mass in all mice, approximately 6 days after the first treatment. The therapeutic response induced by Delta ihfABpmi was accompanied with macrophage accumulation of antitumor phenotype (M1) and significant increase in the mRNAs of proinflammatory mediators (TNF-alpha, IL-6, and iNOS) and an apoptosis inducer (Bax). Our findings indicate that the attenuated Delta ihfABpmi exerts its antitumor activity by inducing macrophage infiltration or reprogramming the immunosuppressed tumor microenvironment to an activated state, suggesting that attenuated S. enterica Typhimurium strains based on nucleoid-associated protein genes deletion could be immunotherapeutic against cancer. (AU)

• Processo FAPESP: 19/17091-5 - Análise fenotípica de macrófagos e histopatologia em camundongos infectados com Leishmania braziliensis
• Beneficiário: Marina Flóro e Silva
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 21/10577-0 - Centro de Pesquisa em Biologia de Bactérias e Bacteriófagos (CEPID B3)
• Beneficiário: Shaker Chuck Farah
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 21/00465-0 - Genômica, patogenicidade, resistência, terapia antitumoral e vacinas baseadas em Salmonella enterica
• Beneficiário: Marcelo Brocchi
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 22/11399-0 - Salmonella enterica e Vesículas de Membrana Externa Como Agente Antitumoral
• Beneficiário: Genesy Perez Jorge
• Modalidade de apoio: Bolsas no Brasil - Programa Capacitação - Treinamento Técnico
• Processo FAPESP: 20/01535-9 - Genômica comparativa e atividade antimicrobiana de endolisinas fágicas recombinantes contra bactérias gram-negativas multirresistentes
• Beneficiário: Marco Túlio Pardini Gontijo
• Modalidade de apoio: Bolsas no Brasil - Mestrado