Needs of Direct Support Professionals to Support People With Intellectual Disabilities in Leading a Healthy Lifestyle

Background For a healthy lifestyle, people with moderate, severe, and profound intellectual disabilities living in residential facilities and/or participating in day activity centers are dependent on their direct support professionals. However, it is unclear what knowledge and skills these direct support professionals require to support these individuals in living a healthy lifestyle. Therefore, the aim of this study was to identify the needs of direct support professionals for supporting these people with moderate to profound intellectual disabilities to achieve and maintain a healthy lifestyle. Method Direct support professionals (n = 28) were interviewed with the use of a semi-structured protocol based on the theoretical domains framework. The interviews were analyzed with a theory-driven content analysis. Results The most frequently mentioned needs referred to the following domains of the theoretical domains framework: environmental context and resources (n = 27), social/professional role and identity (n = 25), social influence (n = 25), skills (n = 24), and knowledge (n = 23). Conclusion To support people with moderate to profound intellectual disabilities in leading a healthy lifestyle, direct support professionals (DSPs) primarily needed support related to the domain environmental context and resources. Within this domain available time, dealing with different seasons, and a healthy lifestyle policy in the organization need attention. Development of interventions targeting these DSPs needs is required

Use of behaviour change techniques by direct support professionals to support healthy lifestyle behaviour for people with moderate to profound intellectual disabilities

Background Behaviour change techniques (BCTs) can be employed to support a healthy lifestyle for people with intellectual disabilities. The aim of this study is to determine whether and which BCTs are used by direct support professionals (DSPs) for supporting healthy lifestyle behaviour of people with moderate to profound intellectual disabilities. Method Direct support professionals (n = 18) were observed in their daily work using audio-visual recordings. To code BCTs, the Coventry Aberdeen London Refined (CALO-RE-NL) taxonomy was employed. Results Direct support professionals used 33 BCTs out of 42. The most used BCTs were as follows: 'feedback on performance', 'instructions on how to perform the behaviour', 'doing together', 'rewards on successful behaviour', 'reward effort towards behaviour', 'DSP changes environment', 'graded tasks', 'prompt practice' and 'model/demonstrate behaviour'. Conclusions Although a variety of BCTs is used by DSPs in their support of people with moderate to profound intellectual disabilities when facilitating healthy lifestyle behaviour, they rely on nine of them

T-Bet and Eomes Regulate the Balance between the Effector/Central Memory T Cells versus Memory Stem Like T Cells

Memory T cells are composed of effector, central, and memory stem cells. Previous studies have implicated that both T-bet and Eomes are involved in the generation of effector and central memory CD8 T cells. The exact role of these transcription factors in shaping the memory T cell pool is not well understood, particularly with memory stem T cells. Here, we demonstrate that both T-bet or Eomes are required for elimination of established tumors by adoptively transferred CD8 T cells. We also examined the role of T-bet and Eomes in the generation of tumor-specific memory T cell subsets upon adoptive transfer. We showed that combined T-bet and Eomes deficiency resulted in a severe reduction in the number of effector/central memory T cells but an increase in the percentage of CD62LhighCD44low Sca-1+ T cells which were similar to the phenotype of memory stem T cells. Despite preserving large numbers of phenotypic memory stem T cells, the lack of both of T-bet and Eomes resulted in a profound defect in antitumor memory responses, suggesting T-bet and Eomes are crucial for the antitumor function of these memory T cells. Our study establishes that T-bet and Eomes cooperate to promote the phenotype of effector/central memory CD8 T cell versus that of memory stem like T cells. © 2013 Li et al

Multifaceted role of BTLA in the control of CD8+ T cell fate after antigen encounter

Purpose: Adoptive T-cell therapy using autologous tumor-infiltrating lymphocytes (TIL) has shown an overall clinical response rate 40%–50% in metastatic melanoma patients. BTLA (B-and-T lymphocyte associated) expression on transferred CD8+ TILs was associated with better clinical outcome. The suppressive function of the ITIM and ITSM motifs of BTLA is well described. Here, we sought to determine the functional characteristics of the CD8+BTLA+TIL subset and define the contribution of the Grb2 motif of BTLA in T-cell costimulation. Experimental Design: We determined the functional role and downstream signal of BTLA in both human CD8+ TILs and mouse CD8+ T cells. Functional assays were used including single-cell analysis, reverse-phase protein array (RPPA), antigen-specific vaccination models with adoptively transferred TCR-transgenic T cells as well as patient-derived xenograft (PDX) model using immunodeficient NOD-scid IL2Rgammanull (NSG) tumor-bearing mice treated with autologous TILs. Results: CD8+BTLA? TILs could not control tumor growth in vivo as well as their BTLA+ counterpart and antigen-specific CD8+BTLA? T cells had impaired recall response to a vaccine. However, CD8+BTLA+ TILs displayed improved survival following the killing of a tumor target and heightened “serial killing” capacity. Using mutants of BTLA signaling motifs, we uncovered a costimulatory function mediated by Grb2 through enhancing the secretion of IL-2 and the activation of Src after TCR stimulation. Conclusions: Our data portrays BTLA as a molecule with the singular ability to provide both costimulatory and coinhibitory signals to activated CD8+ T cells, resulting in extended survival, improved tumor control, and the development of a functional recall response. Clin Cancer Res; 23(20); 6151–64. ©2017 AACR

Detection of Intra-Tumor Self Antigen Recognition during Melanoma Tumor Progression in Mice Using Advanced Multimode Confocal/Two Photon Microscope

Determining how tumor immunity is regulated requires understanding the extent to which the anti-tumor immune response “functions” in vivo without therapeutic intervention. To better understand this question, we developed advanced multimodal reflectance confocal/two photon fluorescence intra-vital imaging techniques to use in combination with traditional ex vivo analysis of tumor specific T cells. By transferring small numbers of melanoma-specific CD8+ T cells (Pmel-1), in an attempt to mimic physiologic conditions, we found that B16 tumor growth alone was sufficient to induce naive Pmel-1 T cell proliferation and acquisition of effector phenotype. Tumor -primed Pmel-1 T cells, are capable of killing target cells in the periphery and secrete IFNγ, but are unable to mediate tumor regression. Within the tumor, Pmel-1 T cells have highly confined mobility, displaying long term interactions with tumor cells. In contrast, adoptively transferred non tumor-specific OT-I T cells show neither confined mobility, nor long term interaction with B16 tumor cells, suggesting that intra-tumor recognition of cognate self antigen by Pmel-1 T cells occurs during tumor growth. Together, these data indicate that lack of anti-tumor efficacy is not solely due to ignorance of self antigen in the tumor microenvironment but rather to active immunosuppressive influences preventing a protective immune response

Use of behaviour change techniques by direct support professionals to support healthy lifestyle behaviour for people with moderate to profound intellectual disabilities

Background: Behaviour change techniques (BCTs) can be employed to support a healthy lifestyle for people with intellectual disabilities. The aim of this study is to determine whether and which BCTs are used by direct support professionals (DSPs) for supporting healthy lifestyle behaviour of people with moderate to profound intellectual disabilities. Method: Direct support professionals (n = 18) were observed in their daily work using audio-visual recordings. To code BCTs, the Coventry Aberdeen London Refined (CALO-RE-NL) taxonomy was employed. Results: Direct support professionals used 33 BCTs out of 42. The most used BCTs were as follows: ‘feedback on performance’, ‘instructions on how to perform the behaviour’, ‘doing together’, ‘rewards on successful behaviour’, ‘reward effort towards behaviour’, ‘DSP changes environment’, ‘graded tasks’, ‘prompt practice’ and ‘model/demonstrate behaviour’. Conclusions: Although a variety of BCTs is used by DSPs in their support of people with moderate to profound intellectual disabilities when facilitating healthy lifestyle behaviour, they rely on nine of them

Targeted calcium influx boosts cytotoxic T lymphocyte function in the tumour microenvironment

Adoptive cell transfer utilizing tumour-targeting cytotoxic T lymphocytes (CTLs) is one of the most effective immunotherapies against haematological malignancies, but significant clinical success has not yet been achieved in solid tumours due in part to the strong immunosuppressive tumour microenvironment. Here, we show that suppression of CTL killing by CD4+CD25+Foxp+ regulatory T cell (Treg) is in part mediated by TGFβ-induced inhibition of inositol trisphosphate (IP3) production, leading to a decrease in T cell receptor (TCR)-dependent intracellular Ca2+ response. Highly selective optical control of Ca2+ signalling in adoptively transferred CTLs enhances T cell activation and IFN-γ production in vitro, leading to a significant reduction in tumour growth in mice. Altogether, our findings indicate that the targeted optogenetic stimulation of intracellular Ca2+ signal allows for the remote control of cytotoxic effector functions of adoptively transferred T cells with outstanding spatial resolution by boosting T cell immune responses at the tumour sites

IL-23 suppresses innate immune response independently of IL-17A during carcinogenesis and metastasis

IL-23 is an important molecular driver of Th17 cells and has strong tumor-promoting proinflammatory activity postulated to occur via adaptive immunity. Conversely, more recently it has been reported that IL-17A elicits a protective inflammation that promotes the activation of tumor-specific CD8(+) T cells. Here we show the much broader impact of IL-23 in antagonizing antitumor immune responses primarily mediated by innate immunity. Furthermore, the majority of this impact was independent of IL-17A, which did not appear critical for many host responses to tumor initiation or metastases. IL-23-deficient mice were resistant to experimental tumor metastases in three models where host NK cells controlled disease. Immunotherapy with IL-2 was more effective in mice lacking IL-23, and again the protection afforded was NK cell mediated and independent of IL-17A. Further investigation revealed that loss of IL-23 promoted perforin and IFN-gamma antitumor effector function in both metastasis models examined. IL-23-deficiency also strikingly protected mice from tumor formation in two distinct mouse models of carcinogenesis where the dependence on host IL-12p40 and IL-17A was quite different. Notably, in the 3'-methylcholanthrene (MCA) induction of fibrosarcoma model, this protection was completely lost in the absence of NK cells. Overall, these data indicate the general role that IL-23 plays in suppressing natural or cytokine-induced innate immunity, promoting tumor development and metastases independently of IL-17A