Background:
Increased IL-6 level, M2 macrophages and PD-1
+
CD8
+
T cells in tumor microenvironments (TME) have been identified to correlate with resistance to checkpoint blockade immunotherapy, yet the mechanism remains poorly understood. Rab small GTPase-mediated trafficking of cytokines is critical in immuno-modulation. We have previously reported dysregulation of Rab37 in lung cancer cells, whereas the roles of Rab37 in tumor-infiltrating immune cells and cancer immunotherapy are unclear.
Methods:
The tumor growth of the syngeneic mouse allograft in wild type or
Rab37
knockout mice was analyzed. Imaging analyses and vesicle isolation were conducted to determine Rab37-mediated IL-6 secretion. STAT3 binding sites at
PD-1
promoter in T cells were identified by chromatin immunoprecipitation assay. Multiplex fluorescence immunohistochemistry was performed to detect the protein level of Rab37, IL-6 and PD-1 and localization of the tumor-infiltrating immune cells in allografts from mice or tumor specimens from lung cancer patients.
Results:
We revealed that Rab37 regulates the secretion of IL-6 in a GTPase-dependent manner in macrophages to trigger M2 polarization. Macrophage-derived IL-6 promotes STAT3-dependent
PD-1
mRNA expression in CD8
+
T cells. Clinically, tumors with high stromal Rab37 and IL-6 expression coincide with tumor infiltrating M2-macrophages and PD1
+
CD8
+
T cells that predicts poor prognosis in lung cancer patients. In addition, lung cancer patients with an increase in plasma IL-6 level are found to be associated with immunotherapeutic resistance. Importantly, combined blockade of IL-6 and CTLA-4 improves survival of tumor-bearing mice by reducing infiltration of PD1
+
CD8
+
T cells and M2 macrophages in TME.
Conclusions:
Rab37/IL-6 trafficking pathway links with IL-6/STAT3/PD-1 transcription regulation to foster an immunosuppressive TME and combined IL-6/CTLA-4 blockade therapy exerts potent anti-tumor efficacy.
Aims
To identify dementia‐friendly communities’ indicators and their current conditions in Taiwan from the perspectives of people with dementia and dementia‐family caregivers.
Design
This qualitative study explored the opinions and experiences of people with dementia and dementia‐family caregivers regarding dementia‐friendly communities.
Methods
Participants (16 people with dementia and 20 family caregivers) were recruited from neurological clinics, day care centres for people with dementia and support groups for family caregivers in the Taipei community from July ‐ October, 2016. Data were collected in face‐to‐face interviews, which were tape recorded and transcribed verbatim. Transcripts were analysed by Miles and Huberman's (1994) guidelines.
Results
Similar indicators for dementia‐friendly communities were identified in Taiwan as in other countries, including dementia‐friendly care services, dementia‐friendly hospitals, dementia‐friendly community environment, dementia‐friendly transportation, dementia‐friendly stores and shops, dementia friendly people, integrated dementia‐related information and community contribution‐ and ‐involvement opportunities for people with dementia. However, Taiwanese people with dementia and family caregivers described no emphasis on the potential of people with dementia to contribute to developing dementia‐friendly communities and more top‐down expectations for the government's role.
Conclusion
These indicators can be a guide for developing and evaluating dementia‐friendly communities in Taiwan. Differences between Taiwan and Western developed countries in indicators for dementia‐friendly communities can be further explored. Community nursing assessment, interventions, and evaluation based on these dementia‐friendly communities indicators can be further developed.
Impact
This study developed indicators for dementia‐friendly communities in an Asian country. These indicators can be used as a guide for developing and evaluating dementia‐friendly communities.
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