Abstract 1181: Therapeutic efficacy by Streptococcus salivarius as a probiotic in a preclinical model of oropharyngeal carcinoma
Authors: Diaz Jennifer , Rivera Michael , Del Valle Kamila A. , Piñero Edna E. , Vitorino Filipa , Ortiz Jorge R. , Estremera Stephanie M. 
Published: March 2024

Abstract
Streptococcus salivarius is a gram-positive, non-pathogenic bacteria found in the oral cavity and upper respiratory tract. This bacterium has been shown to possess antimicrobial properties with the potential to cause activation of natural killer (NK) cells and induction of anti-tumorigenic cytokines such as interferon-gamma and interleukin-12 (IL-12). There is a high abundance of this bacteria in the saliva in oral squamous cell carcinoma patients. Moreover, Streptococcus-reactive cytotoxic T cells were associated with recurrence-free survival. Nevertheless, there is a considerable lack of information regarding the impact of S. salivarius on intratumoral immune responses and its potential as a cancer therapeutic. This study aimed to characterize the immune responses in the tumor microenvironment by S. salivarius in combination with programmed cell death protein 1 (anti-PD-1) therapy and its therapeutic efficacy. We expect that S. salivarius will cooperate with immune checkpoint inhibitors, activating antitumor immune responses. For this project, we used a preclinical murine model where an HPV+ oropharyngeal cancer cell line named mEER was implanted subcutaneously or in the tongue of the mice. We treated with or without S. salivarius and/or anti-PD-1. First, S. salivarius was administered intratumorally on subcutaneous tumors and treated or not with anti-PD-1 therapy administered intraperitoneally. We measured tumor volume and quantified different immune cells by flow cytometry. While anti-PD-1 treated mice showed a continuous increase in tumor volume, the ones treated with anti-PD-1 and S. salivarius reduced the growth rate starting at day 20. Mice treated with anti-PD1 and S. salivarius showed increased CD4+ T cells and myeloid-derived suppressor cells (MDSCs) compared to anti-PD-1 treatment alone. Secondly, we implanted the mice with tongue tumors and applied S. salivarius topically in the oral cavity with or without anti-PD-1. The use of S. salivarius contributed to an increase in CD4+T cells and activation of CD8+T cells and NK cells. The combination of anti-PD-1 with S. salivarius did not further enhance the activation of these cells. Nevertheless, 80% of mice receiving anti-PD-1 with S. salivarius responded to the therapy, whereas 63% responded while receiving only anti-PD-1. In conclusion, Streptococcus salivarius as a probiotic, affected tumor development and immune cell infiltration in oropharyngeal cancer. Future analyses will allow us to explore the effect of the probiotic on the tumor microenvironment and improve colonization in the oral cavity.
Citation Format: Jennifer Diaz, Michael Rivera, Kamila A. Del Valle, Edna E. Piñero, Filipa Vitorino, Jorge R. Ortiz, Stephanie M. Estremera. Therapeutic efficacy by Streptococcus salivarius as a probiotic in a preclinical model of oropharyngeal carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1181.