Neoantigen-specific CD4+ T cells in human melanoma have diverse differentiation states and correlate with CD8+ T cell, macrophage, and B cell function.

CD4+ T cells that recognize tumor antigens are required for immune checkpoint inhibitor efficacy in murine models, but their contributions in human cancer are unclear. We used single-cell RNA sequencing and T cell receptor sequences to identify signatures and functional correlates of tumor-specific CD4+ T cells infiltrating human melanoma. Conventional CD4+ T cells that recognize tumor neoantigens express CXCL13 and are subdivided into clusters expressing memory and T follicular helper markers, and those expressing cytolytic markers, inhibitory receptors, and IFN-γ. The frequency of CXCL13+ CD4+ T cells in the tumor correlated with the transcriptional states of CD8+ T cells and macrophages, maturation of B cells, and patient survival. Similar correlations were observed in a breast cancer cohort. These results identify phenotypes and functional correlates of tumor-specific CD4+ T cells in melanoma and suggest the possibility of using such cells to modify the tumor microenvironment.

Efficacy of Motivational Interviewing in Treating Co-occurring Psychosis and Substance Use Disorder: A Systematic Review and Meta-Analysis.

Objective: A wealth of evidence has supported the efficacy of motivational interviewing (MI) in reducing substance use as well as other addictive behaviors. In view of the common co-occurrence of substance use disorder among individuals with schizophrenia spectrum disorders, there has been increased attention to applying MI in psychological interventions for individuals with co-occurring psychosis and substance use disorder. This review aims to synthesize the evidence on the efficacy of MI interventions (either as a stand-alone intervention or in combination with other psychological interventions) in reducing substance use and psychotic symptoms.Data Sources: MEDLINE, PsycINFO, EMBASE, CENTRAL, and CINAHL were searched using keywords related to "psychosis," "substance addiction," and "motivational interviewing" to identify studies published in English from 1984 to May 2021.Study Selection: Of 1,134 articles identified in the literature, we selected 17 studies for review: 5 studies examined stand-alone MI ("MI-pure"), and 13 studies assessed MI as a major treatment component ("MI-mixed").Data Extraction: Demographics of participants, intervention characteristics, and outcome data were extracted by the first author and checked by the second author. Random-effects models were used for substance use and psychotic symptom outcomes.Results: MI-pure interventions did not significantly reduce severity of substance use (g = 0.06, P = .81) or psychotic symptoms (g's for 2 individual studies = 0.16, P = .54; and 0.01, P = .96). The effect of MI-mixed interventions on substance use decrease was statistically significant but small in size (g = 0.15, P = .048), whereas the effect on psychotic symptom improvement was not significant (g = 0.11, P = .22).Conclusions: With the caveat that only a small number of comparisons were available for the review on MI-pure interventions, the efficacy of MI in treating co-occurring psychosis and substance use disorder was heterogeneous and modest.

Anti-PD-L1 antibody direct activation of macrophages contributes to a radiation-induced abscopal response in glioblastoma.

BACKGROUND: Most glioblastomas recur near prior radiation treatment sites. Future clinical success will require achieving and optimizing an "abscopal effect," whereby unirradiated neoplastic cells outside treatment sites are recognized and attacked by the immune system. Radiation combined with anti-programmed cell death ligand 1 (PD-L1) demonstrated modest efficacy in phase II human glioblastoma clinical trials, but the mechanism and relevance of the abscopal effect during this response remain unknown. METHODS: We modified an immune-competent, genetically driven mouse glioma model (forced platelet derived growth factor [PDGF] expression + phosphatase and tensin homolog loss) where a portion of the tumor burden is irradiated (PDGF) and another unirradiated luciferase-expressing tumor (PDGF + luciferase) is used as a readout of the abscopal effect following systemic anti-PD-L1 immunotherapy. We assessed relevance of tumor neoepitope during the abscopal response by inducing expression of epidermal growth factor receptor variant III (EGFRvIII) (PDGF + EGFRvIII). Statistical tests were two-sided. RESULTS: Following radiation of one lesion, anti-PD-L1 immunotherapy enhanced the abscopal response to the unirradiated lesion. In PDGF-driven gliomas without tumor neoepitope (PDGF + luciferase, n = 8), the abscopal response occurred via anti-PD-L1 driven, extracellular signal-regulated kinase-mediated, bone marrow-derived macrophage phagocytosis of adjacent unirradiated tumor cells, with modest survival implications (median survival 41 days vs radiation alone 37.5 days, P = 0.03). In PDGF-driven gliomas with tumor neoepitope (PDGF + EGFRvIII, n = 8), anti-PD-L1 enhanced abscopal response was associated with macrophage and T-cell infiltration and increased survival benefit (median survival 36 days vs radiation alone 28 days, P = 0.001). CONCLUSION: Our results indicate that anti-PD-L1 immunotherapy enhances a radiation- induced abscopal response via canonical T-cell activation and direct macrophage activation in glioblastoma.

Cognitive-behavioral group program for Chinese heterosexual HIV-infected men in Hong Kong.

This study explored the effects of cognitive-behavioral program (CBP) using a wait-list control group in 16 Chinese heterosexual HIV-infected men. Participants in the treatment condition underwent a 7-week group based CBP, which addressed various HIV-related issues. Relevant cognitive and behavioral strategies were taught as well. The aim of treatment was to improve the quality of life and to reduce psychological distress in a sample of heterosexual symptomatic HIV-infected men. Prior to intervention, baseline measures showed that our sample had a lower quality of life in comparison with the local general population. They also experienced a significant level of psychological distress. Following intervention, men in the CBP group demonstrated significant improvement in the mental health dimension of quality of life and a significant reduction in depressed mood. These preliminary findings suggested that short-term cognitive-behavioral therapy can be effective in improving the quality of life and mood of Chinese heterosexual HIV-infected men.