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

Patients’ Perception of Patient–Provider Communication in Fertility Preservation Decision Making Among Young Women With Cancer

Fertility preservation (FP) for patients with cancer is an emerging field. With the advancement of technology, patients may face a complex decision-making process about whether to preserve fertility. The purpose of this article is to explore how young women with cancer perceive patient–provider communication in FP decision making. In this study, 25 women between the ages of 18 and 39 were interviewed retrospectively. They were interviewed one time to learn about their decision-making process related to FP. Results of this analysis indicate that patients seek support and involvement from providers throughout the process of decision making. They prefer providers to be directive when referring to the fertility clinic. Later in the process, they expect a supportive style of communication from providers. Patient-accessible language, supportive and reassuring styles of communication, and an existing relationship with providers may enhance well-being of the patients

Identifying Factors Associated With Falls in Postmenopausal Breast Cancer Survivors: A Multi-Disciplinary Approach

Objective—To identify neuromuscular, balance and vision factors that contribute to falls in recently treated breast cancer survivors (BCS) and explore links between fall risk factors and cancer treatment Design—Case-control plus prospective observation Setting—Comprehensive cancer center Participants—BCS within two years chemotherapy completion and/or on adjuvant endocrine therapy (N=59; mean age: 58 yrs) Intervention—not applicable Main outcome measures—Objective measures of postural control, vision and neuromuscular function included 1) a sensory organization test (SOT), 2) a visual assessment battery, 3) muscle mass by DXA, and 4) neuromuscular function with strength by repetition maximum, power by timed stair climb, and gait speed by 4m walk. Falls were self-reported for the past year (retrospective) and monthly for six months (prospective). Results—58% of BCS reported falls in the past year. BCS with a history of falls had lower SOT scores with a vestibular deficit pattern in postural control (