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

Informative Disagreements: Associations Between Relationship Distress, Depression, and Discrepancy in Interpersonal Perception Within Couples

This study evaluated the associations between relationship distress, depression symptoms, and discrepancy in interpersonal perception within couples. After completing a series of discussion tasks, couples (N = 88) rated their behavior using the circumplex‐based Structural Analysis of Social Behavior Model (SASB; Benjamin, 1979, 1987, 2000). Overall, couple members were strikingly similar in their interpersonal perceptions, and tended to see themselves as friendly, reciprocal in their focus, and balanced between connection and separateness. As hypothesized, however, perceptual discrepancy was related to relationship distress and depression. Relationship distress was associated with discrepancy regarding transitive behavior focused on the partner, while depression was associated with disagreement about intransitive, self‐focused behavior. Analysis of affiliation and autonomy revealed that relationship distress was associated with seeing oneself as reacting with more hostility than the partner sees, and perceiving one\u27s partner as more hostile, more controlling, and less submissive than he or she does. Partners of depressed individuals viewed themselves as more controlling than their mate did. Men\u27s depression was associated with disagreement between partners regarding men\u27s self‐focused behavior. Results underscore the importance of considering interpersonal perception when conceptualizing relationship distress and depression within intimate relationships

Organizational Factors Influencing the Early Implementation Process of Diabetes Group Visits by Five Midwestern Community Health Centers: A Multisite Case Study Analysis

The objective was to identify facilitators and challenges of implementing diabetes group visits in 5 Midwestern community health center (CHC) settings that care for diverse patient populations. Interview data were collected from July to August 2015. An interview guide was developed to explore health center teams' initial experiences with diabetes group visit implementation. Interviews were conducted with 14 individuals who participated in a training prior to diabetes group visit implementation. Four levels of coding (open, in vivo, categorical, and thematic) were used to identify characteristics of group visit implementation in 5 CHCs. A semi-structured model encouraged interprofessional teamwork across all CHC teams. Self-appointed or chosen team champions were the "pulse" or central driving force of implementation. A designated time in the clinic for patients to receive education and psychosocial support enhanced engagement in diabetes self-management. Early buy-in from upper leadership was critical to securing fiscal and human resources as unexpected needs emerged during group visit implementation. Time commitment of clinic staff and providers for ongoing operations, socioeconomic challenges of patients, staff turnover, and billing were reported as challenges in the initial implementation process. This study acknowledges the influence of administrative and sociocultural factors on successful implementation of diabetes group visits. Future research should further explore how these factors influence successful adoption of diabetes group visits in health centers across the United States and the impact of group visit implementation on staff and patient outcomes

Population-Level Portal-Based Anxiety and Depression Screening Perspectives in HIV Care Clinicians: Qualitative Study Using the Consolidated Framework for Implementation Research

Background: Depression and anxiety are common among people with HIV and are associated with inadequate viral suppression, disease progression, and increased mortality. However, depression and anxiety are underdiagnosed and undertreated in people with HIV owing to inadequate visit time and personnel availability. Conducting population-level depression and anxiety screening via the patient portal is a promising intervention that has not been studied in HIV care settings. Objective: We aimed to explore facilitators of and barriers to implementing population-level portal-based depression and anxiety screening for people with HIV. Methods: We conducted semistructured hour-long qualitative interviews based on the Consolidated Framework for Implementation Research with clinicians at an HIV clinic. Results: A total of 10 clinicians participated in interviews. In total, 10 facilitators and 7 barriers were identified across 5 Consolidated Framework for Implementation Research domains. Facilitators included advantages of systematic screening outside clinic visits; the expectation that assessment frequency could be tailored to patient needs; evidence from the literature and previous experience in other settings; respect for patient privacy; empowering patients and facilitating communication about mental health; compatibility with clinic culture, workflows, and systems; staff beliefs about the importance of mental health screening and benefits for HIV care; engaging all clinic staff and leveraging their strengths; and clear planning and communication with staff. Barriers included difficulty in ensuring prompt response to suicidal ideation; patient access, experience, and comfort using the portal; limited availability of mental health services; variations in how providers use the electronic health record and communicate with patients; limited capacity to address mental health concerns during HIV visits; staff knowledge and self-efficacy regarding the management of mental health conditions; and the impersonal approach to a sensitive topic. Conclusions: We proposed 13 strategies for implementing population-level portal-based screening for people with HIV. Before implementation, clinics can conduct local assessments of clinicians and clinic staff; engage clinicians and clinic staff with various roles and expertise to support the implementation; highlight advantages, relevance, and evidence for population-level portal-based mental health screening; make screening frequency adaptable based on patient history and symptoms; use user-centered design methods to refine results that are displayed and communicated in the electronic health record; make screening tools available for patients to use on demand in the portal; and create protocols for positive depression and anxiety screeners, including those indicating imminent risk. During implementation, clinics should communicate with clinicians and clinic staff and provide training on protocols; provide technical support and demonstrations for patients on how to use the portal; use multiple screening methods for broad reach; use patient-centered communication in portal messages; provide clinical decision support tools, training, and mentorship to help clinicians manage mental health concerns; and implement integrated behavioral health and increase mental health referral partnerships.</p

Patient Perspectives on Portal-Based Anxiety and Depression Screening in HIV Care: A Qualitative Study Using the Consolidated Framework for Implementation Research

Electronic patient portals represent a promising means of integrating mental health assessments into HIV care where anxiety and depression are highly prevalent. Patient attitudes toward portal-based mental health screening within HIV clinics have not been well described. The aim of this formative qualitative study is to characterize the patient-perceived facilitators and barriers to portal-based anxiety and depression screening within HIV care in order to inform implementation strategies for mental health screening. Twelve adult HIV clinic patients participated in semi-structured interviews that were audio recorded and transcribed. The transcripts were coded using constructs from the Consolidated Framework for Implementation Research and analyzed thematically to identify the barriers to and facilitators of portal-based anxiety and depression screening. Facilitators included an absence of alternative screening methods, an approachable design, perceived adaptability, high compatibility with HIV care, the potential for linkage to treatment, an increased self-awareness of mental health conditions, the ability to bundle screening with clinic visits, and communicating an action plan for results. The barriers included difficulty navigating the patient portal system, a lack of technical support, stigmatization from the healthcare system, care team response times, and the novelty of using patient portals for communication. The patients in the HIV clinic viewed the use of a portal-based anxiety and depression screening tool as highly compatible with routine HIV care. Technical difficulties, follow-up concerns, and a fear of stigmatization were commonly perceived as barriers to portal use. The results of this study can be used to inform implementation strategies when designing or incorporating portal-based mental health screening into other HIV care settings