31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Addressing Breast Cancer Health Disparities in the Mississippi Delta Through an Innovative Partnership for Education, Detection, and Screening

Projects to reduce disparities in cancer treatment and research include collaborative partnerships and multiple strategies to promote community awareness, education, and engagement. This is especially needed in underserved areas such as the Mississippi Delta where more women are diagnosed at regional and distant stages of breast cancer. The purpose for this project was to increase the relatively low screening rate for African American women in the Mississippi Delta through a partnership between the Mississippi Network for Cancer Control and Prevention at The University of Southern Mississippi, The Fannie Lou Hamer Cancer Foundation and the Mississippi State Department of Health to decrease health disparities in breast cancer through increased awareness on self-early detection methods, leveraging resources to provide mammography screenings, and adequate follow-up with services and treatment for abnormal findings. Through this collaborative effort, over 500 women in three rural Mississippi Delta counties were identified, provided community education on early self-detection, and given appointments for mammography screenings within one fiscal year

The Community Health Advisor Program and the Deep South Network for Cancer Control - Health Promotion Programs for Volunteer Community Health Advisors

The Community Health Advisor program is a proven, community-driven health promotion program that identifies and trains natural helpers who then seek to improve the health of individuals and their communities. This article details the basis of the Community Health Advisor model and describes early pilot programs in the Mississippi Delta. Also described is the formation of the Community Health Advisor Network, which provides technical assistance to Community Health Advisor programs and the proliferation of Community Health Advisor programs nationally. Specifically, details are presented of the modification of the model for the Deep South Network for Cancer Control and of early findings showing a decrease in health disparities in Alabama

African American Community Health Advisors Trained As Research Partners - Recruitment and Training

The African American community has played an influential role in generating change. Grass-roots organizations and concerned individuals can be included in programs designed to increase cancer awareness and cancer early detection practices to ultimately eliminate cancer disparities. The utilization of a formalized Community Health Advisors program can be an infrastructure by which effective cancer prevention and control programs can be conducted in underserved African American communities. The purpose of this article is to outline the steps necessary to develop an infrastructure for recruitment and training of grass-root African Americans to serve as Community Health Advisors trained as Research Partners

The Deep South Network for Cancer Control - Eliminating Cancer Disparities Through Community-Academic Collaboration

African Americans have a substantially increased mortality rate compared to whites in many cancers, including breast and cervix. The Deep South Network for Cancer Control (the Network) was established to develop sustainable community infrastructure to promote cancer awareness, enhance participation of African Americans and other special populations in clinical trials, recruit and train minority investigators, and develop and test innovative community-based cancer control measures to eliminate cancer mortality disparities in special populations. This article describes the steps necessary to form the network and the process and activities required to establish it as an effective infrastructure for eliminating disparities between Whites and African Americans in the United States