Association of changes in vaginal microbiome with oligoclonal T-cell expansion and early response to chemoradiation for cervical cancer.

Abstract

8 Background: The composition of the vaginal microbiome has been shown to affect clearance of HPV virus and transformation to invasive cancer. Clinical studies correlating the vaginal microbiome with immune activation and response to cancer treatment are lacking. We profiled intratumoral T-cell clonality during radiation therapy and correlated it with the diversity of the vaginal flora. Methods: Thirty patients with newly diagnosed locally advanced cervical cancer were enrolled on a prospective study to characterize changes in the cervical microbiome during chemoradiation. Cervical samples were obtained before radiation therapy and during the 1st, 3rd, and 5th week of radiation therapy. The vaginal microbiome was characterized using 16 sRNA gene sequencing to produce operational taxonomic units (OTU’s) representing individual bacterial species. Disease response was categorized as early response (ER), late response (LR), or nonresponse (NR) on the basis of clinical examination at brachytherapy and 3-month PET/CT. Twenty patients had T-cell receptor β sequencing of DNA performed using the ImmunoSEQ platform. The maximum productive frequency of the top three clones (MP3) was used to assess T-cell clonality. Results: Early response was associated with clonal T-cell expansion with an increase of MP3 of 11.1% during treatment as compared to a decline of 6.1% in patients with LR/NR (p = 0.05). Early response was also associated with lower quantity of observed OTU’s of vaginal microbiota (25.0 [SD 12.68]) vs patients with LR/NR (41.15 [SD = 23.3]) (p = 0·03). Increased MP3 was associated with increased abundance of Corynebacteriales (R = 0.90; p < .0001) , Actinomycetales (R = 0.83; p < .0001) and Bifidobacteriales (R = 0.82; p < .0001) . Decreased MP3 was associated with increased abundance of lactobacillus (R = -0.61; p < .0001). Conclusions: Increased diversity of the vaginal microbiome is negatively associated with outcome, supporting previous clinical studies in non-cancer settings. Specific vaginal bacterial species are associated with increased or decreased T-cell clonality at completion of radiation.