Cancer Center Support Grant

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Women with HIV and cervical cancer are more likely to suffer a relapse and recurrence of cervical cancer. Treatment factors may contribute to this elevated risk for women with HIV, but an immunosuppressive tumor environment may also be a critical and modifiable factor. We have developed non-invasive assays to characterize the tumor microenvironment in patients in the US and Botswana which will enable us to test the hypothesis that an immunosuppressive microenvironment characterizes HIV associated cervical cancers. We propose to expand the collaboration between Botswana and the US, collecting cervical cancer swabs for serial TCR sequencing and microbiome analysis in both sites. We hypothesize that the immunosuppressive microbiome that we have characterized in Houston patients may also be present in women with cervical cancer in Botswana. Additionally, we hypothesize that less diversity is present in T-cells from cervical cancers in patients with HIV, that clonal T-cell expansion may be impaired in patients with HIV, fewer HPV reactive clones may be present and that these changes may account for reduced rates of survival. To accomplish this, we propose the following specific aims: Specific Aim #1: Determine the abundance of Lactobacillus inners in patients with cervical cancer in Botswana and its associated with treatment response and HIV status. Specific Aim #2: Assess immune activation through TCR sequencing performed at baseline and after 5 weeks of radiation. These findings may lead directly to microbiota interventions aimed at improving response in HIV positive cervical cancer patients. To identify interventions which are broadly relevant and are mostly likely to be successful, a deep understanding of the critical elements of the microbiome and anti-tumor immunity in patients with and without HIV is needed. By leveraging an existing collaboration and established workflow, we can make significant progress in understanding the role of the tumor microbiome in cervical cancer patients with and without HIV