ALBERT

Description: The current study examined clinical correlates of food addiction among post-operative bariatric surgery patients, compared the clinical characteristics of patients with versus without food addiction, and examined whether a brief telephone-based cognitive behavioural therapy (Tele-CBT) intervention improves food addiction symptomatology among those with food addiction. Participants (N = 100) completed measures of food addiction, binge eating, depression, and anxiety 1 year following bariatric surgery, were randomized to receive either Tele-CBT or standard bariatric post-operative care, and then, repeated the measure of food addiction at 1.25 and 1.5 years following surgery. Thirteen percent of patients exceeded the cut-off for food addiction at 1 year post-surgery, and this subgroup of patients reported greater binge eating characteristics and psychiatric distress compared to patients without food addiction. Among those with food addiction, Tele-CBT was found to improve food addiction symptomatology immediately following the intervention. These preliminary findings suggest that Tele-CBT may be helpful, at least in the short term, in improving food addiction symptomatology among some patients who do not experience remission of food addiction following bariatric surgery; however, these findings require replication in a larger sample.

Description: Bariatric surgery remains the most effective treatment for severe obesity, though post-surgical outcomes are variable with respect to long-term weight loss and eating-related psychopathology. Attachment style is an important variable affecting eating psychopathology among individuals with obesity. To date, studies examining eating psychopathology and attachment style in bariatric surgery populations have been limited to pre-surgery samples and cross-sectional study design. The current prospective study sought to determine whether attachment insecurity is associated with binge eating, emotional eating, and weight loss outcomes at 2-years post-surgery. Patients (n = 108) completed questionnaires on attachment style (ECR-16), binge eating (BES), emotional eating (EES), depression (PHQ-9), and anxiety (GAD-7). Multivariate linear regression analyses were conducted to examine the association between attachment insecurity and 2-years post-surgery disordered eating and percent total weight loss. Female gender was found to be a significant predictor of binge eating (p = 0.007) and emotional eating (p = 0.023) at 2-years post-surgery. Avoidant attachment (p = 0.009) was also found to be a significant predictor of binge eating at 2-years post-surgery. To our knowledge, this study is the first to explore attachment style as a predictor of long-term post-operative eating pathology and weight outcomes in bariatric surgery patients.

Description: BACKGROUND: Multiple myeloma (MM) is the most common indication for high-dose chemotherapy and autologous stem cell transplantation (ASCT). Post-transplant lenalidomide maintenance therapy doubles progression-free survival, but almost all patients eventually relapse. The immune system participates in the control of MM, whereas compromised immunity contributes to its evolution. Post-transplant immunotherapy to induce or restore antitumor immunity offers a promising approach to target residual MM and improve patient outcomes. The rational development of immunotherapeutic interventions after ASCT, however, requires a comprehensive understanding of the immunologic milieu. We therefore evaluated lymphocyte composition and function after ASCT to guide optimal timing of immunotherapy and to identify potential markers of relapse. METHODS: Fifty-five MM patients undergoing ASCT were evaluated for at least one year. Peripheral blood from patients was obtained before ASCT and on d +12, +30, +90, +180, and +365 after ASCT, and at the time of relapse where applicable. Leukocyte concentrates were used as a source of healthy donor cells. Mononuclear cells were analyzed by flow cytometry for phenotypic assessment of lymphocyte subset composition. Functional assessment of dendritic cell and T cell activity in vitro was assayed in autologous and allogeneic mixed leukocyte reactions, cytotoxic T lymphocyte (CTL) lysis assays, and PD-1 blockade experiments. RESULTS: CD3+ CD4+ CD25bright CD127neg regulatory T cells (Tregs) decline as CD8+ T cells expand during early lymphocyte recovery after ASCT, markedly reducing the Treg:CD8+ effector T-cell ratio (Fig 1A) and providing a critical early window for the introduction of immune-based post-transplant consolidation therapies. CD8+ T cells can respond to autologous dendritic cells presenting tumor antigen in vitro as early as day +12 post-transplant, becoming antigen-specific CTL effectors and thereby demonstrating preservation of cellular reactivity (Fig 1B). CD4+ and CD8+ T cells express the negative regulatory molecules, CTLA-4, PD-1, LAG-3, and TIM-3, before and after ASCT (data not shown). A subpopulation of exhausted/senescent CD8+ T cells, however, down-regulates CD28 (Fig 2A) and up-regulates CD57 (Fig 2B) and PD-1 (Fig 2C), characterizing immune impairment and relapse after ASCT. CD4+ T cells show the same trends in the frequencies of CD28neg, CD28neg CD57+, and CD28neg PD-1+ cells, albeit at lower levels of expression (Fig 2D). Relapsing patients have higher numbers of CD8+ CD28neg PD-1+ T cells at +3 months after transplant (Fig 2E), but before detection of clinical disease, indicating their applicability in identifying patients at higher risk of relapse. PD-1 blockade revives the proliferation and cytokine secretion of the hyporesponsive, CD8+ CD28neg PD-1+ T cells in vitro (Fig 3). CONCLUSION: These results identify T cell exhaustion/senescence as a distinguishing feature of relapse and support early introduction of immunotherapy to stimulate antitumor immunity after ASCT. Disclosures Lesokhin: Genentech: Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Aduro: Consultancy; Janssen: Consultancy, Research Funding; Efranat: Consultancy. Giralt:CELGENE: Consultancy, Honoraria, Research Funding; SANOFI: Consultancy, Honoraria, Research Funding; AMGEN: Consultancy, Research Funding; JAZZ: Consultancy, Honoraria, Research Funding, Speakers Bureau; TAKEDA: Consultancy, Honoraria, Research Funding.

Description: The concept of food addiction has generated much controversy. In comparison to research examining the construct of food addiction and its validity, relatively little research has examined the broader implications of food addiction. The purpose of the current scoping review was to examine the potential ethical, stigma, and health policy implications of food addiction. Major themes were identified in the literature, and extensive overlap was identified between several of the themes. Ethics sub-themes related primarily to individual responsibility and included: (i) personal control, will power, and choice; and (ii) blame and weight bias. Stigma sub-themes included: (i) the impact on self-stigma and stigma from others, (ii) the differential impact of substance use disorder versus behavioral addiction on stigma, and (iii) the additive stigma of addiction plus obesity and/or eating disorder. Policy implications were broadly derived from comparisons to the tobacco industry and focused on addictive foods as opposed to food addiction. This scoping review underscored the need for increased awareness of food addiction and the role of the food industry, empirical research to identify specific hyperpalatable food substances, and policy interventions that are not simply extrapolated from tobacco.

Description: Background: Mycosis fungoides (MF) and Sézary syndrome (SS) represent the most common types of cutaneous T-cell lymphoma (CTCL). CTCL develops from clonally-expanded, effector/central memory CD4+ T cells in a background of chronic inflammation. The eliciting Ag(s) and how this inflammation contributes to the development and progression of CTCL remain important unknowns. Despite tumor-infiltrating CD8+ T cells in skin, the malignant CD4+ T-cell population persists, indicating that these CD8+ T cells cannot exert an effective anti-tumor response, potentially due to T-cell exhaustion, which has been observed in chronic viral infections and is associated with disease progression in hematologic malignancies like ATLL and CLL. Exhausted T-cells are characterized by immunoinhibitory molecules, like programmed death-1 (PD-1). Engagement of PD-1 by PD-Ligand (L)-1/L-2 transduces a signal that leads to inhibition of T-cell functions, but the cells are not deleted. PD-L1 is expressed on T cells, dendritic cells (DCs), and many tumor cells, whereas PD-L2 expression is limited to antigen-presenting cells. Although malignant CD4+ T cells in Sézary syndrome lesions express PD-1, the relevance of the PD-1/PD-L1/2 pathway in CTCL and the immune cells in CTCL that express PD-L1/L2 are not known. Methods: Epidermis and dermis of skin biopsies from consented CTCL pts (12) and healthy donors (3) were separated using dispase-II and incubated in RPMI-10% pooled human serum for 24 hrs. Migrated cutaneous T cells and DCs were phenotyped by flow cytometry for a variety of maturation markers and immune checkpoint molecules. In 3 pts skin findings were compared with matched PBMCs. Results: Freshly isolated cutaneous CD8+ T cells displayed distinct effector and memory subsets with a higher frequency of effector-memory (CD28-CD45RA-CCR7-) and terminally differentiated effector cells (CD28-CD45RA+CCR7-). In addition, CD8+ T-cells exhibited enhanced expression of PD-1, Lag-3, Tim-3, and ICOS. PD-1 was the receptor most overexpressed in CD8+ T cells compared with healthy controls. PD-1 expression on circulating CD8+ T cells was lower compared with skin-infiltrating CD8+ T-cells. In contrast, the malignant CD4+ T-cells expressed predominantly a central memory or transient memory subtype (CD28+CD45RA-CCR7+/-), with overexpression of PD-1, CTLA-4, Lag-3, and ICOS. Immune-suppressive CD3+CD4+FoxP3+CD127-Tregs were not increased in PBMCs of CTCL pts. Migrated DCs displayed an activated, mature phenotype expressing HLA-DR+, CD1a+/-, CD207 (Langerin)+/-, CD14+/-, CD11c+, CD83low/med, CD86low/med and PD-L1+/- phenotype. Conclusion: Both the malignant CD4+ T cells and tumor-infiltrating CD8+ T cells display an exhausted phenotype, while DC subsets display a normal activated phenotype. Our preliminary data imply a role for PD-1 and other checkpoint molecules like ICOS, Tim-3, Lag-3 in attenuating the anti-tumor response. Studies are underway in vitro to establish the function of PD-1, Lag-3, Tim-3, and ICOS on T cells in response to DC/LC stimulation to develop a rationale for therapeutic checkpoint blockade inhibitors to reverse the exhausted T cell phenotype and attendant lack of immune reactivity. Disclosures No relevant conflicts of interest to declare.