Place, People, and Health: Korean Apartment Residents' Experiences of Local Social Relationships and Their Effects on Mental Health and Well-being

Thesis (Ph.D.)--University of Washington, 2019How can neighborhood environment affect residents’ mental health and well-being? In the broad context of understanding this mechanism, this dissertation focuses on the residents’ social relationships based on the neighborhood and their effects on mental health and well-being. Concentrating on the experiences of the apartment residents in Pangyo, Seoul metropolitan area, Korea, this study discusses and seeks answers to the following questions: 1) what are the nature/characteristics (essences) of experienced local social relationships of residents in the neighborhood which consists of multi-layered high-rise apartment complexes; 2) how do spatial characteristics of such residential settings contribute to the experiences of local social relationships; and 3) how do residents’ experiences of local social relationships from their everyday living environment contribute to their mental health and well-being. Through a phenomenological research, including dialogical-conversational interviews and thematic analysis, the discourse of twenty-eight women residents about their years of experiences in the neighborhood were explored. Except for the relations established through local institutions, participants formed their relations with their neighbors by repetitively encountering them in and around the apartment complexes. The spatial settings of apartment complexes, however, did not actively support these place-based encounters because of the highly compartmentalized spatial structures with a short moving line. Thus, the places of possible encounters were generally limited to the common use spaces which participants had to pass through in the course of their everyday lives — such as the elevators, and the entrance areas of the buildings and the underground parking lots. The local social relations experienced by participants have both positive and negative effects on their mental health and well-being. In other words, local social relationships are multifaceted and have complex relationship with health. Participants found that the existence of neighbors and interactions with them contributed to their mental health and well-being. They received emotional social support, which helped them cope with daily stress and keep positive mood, from their intimate neighbors and generally positive relationships with neighbors. They also received diverse instrumental support from their local social networks thanks to the physical proximity and related immediacy. Participants had mostly shallow relationships with their neighbors and further they had generally low sense of belonging to their everyday living place, but these experiences did not seem to have strong effects on their mental health and well-being within the socioeconomic context of this neighborhood. However, the superficiality of social relationships which primarily centered around participants’ children rather than themselves, was experienced as stressful. These relations seemed to have negative effects on mental well-being, interlinking with the competitive children education and related comparisons. The general social comparisons between neighbors, beyond the education issue, also made participants feel inferiority and stressful

Impact of anatomic site on antigen-presenting cells in cancer

Checkpoint blockade immunotherapy (CBT) can induce long-term clinical benefits in patients with advanced cancer; however, response rates to CBT vary by cancer type. Cancers of the skin, lung, and kidney are largely responsive to CBT, while cancers of the pancreas, ovary, breast, and metastatic lesions to the liver respond poorly. The impact of tissue-resident immune cells on antitumor immunity is an emerging area of investigation. Recent evidence indicates that antitumor immune responses and efficacy of CBT depend on the tissue site of the tumor lesion. As myeloid cells are predominantly tissue-resident and can shape tumor-reactive T cell responses, it is conceivable that tissue-specific differences in their function underlie the tissue-site-dependent variability in CBT responses. Understanding the roles of tissue-specific myeloid cells in antitumor immunity can open new avenues for treatment design. In this review, we discuss the roles of tissue-specific antigen-presenting cells (APCs) in governing antitumor immune responses, with a particular focus on the contributions of tissue-specific dendritic cells. Using the framework of the Cancer-Immunity Cycle, we examine the contributions of tissue-specific APC in CBT-sensitive and CBT-resistant carcinomas, highlight how these cells can be therapeutically modulated, and identify gaps in knowledge that remain to be addressed

Regulation of tumor growth by leukocyte-specific protein 1 in T cells

Background Clinical efficacy of T cell-based cancer immunotherapy is limited by the lack of T cell infiltration in the tumor mass, especially in solid tumors. Our group demonstrated previously that leukocyte-specific protein 1 (LSP1), an intracellular signal regulator, negatively regulates T cell infiltration in inflamed tissues.Methods To determine the immuno-regulatory effects of LSP1 in T cells on tumor progression, we investigated the growth of B16 melanoma in Lsp1 knockout (KO) mice and T cell-specific Lsp1 transgenic (Tg) mice. The immune cell subpopulation infiltrated into the tumor mass as well as the expression of interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) in T cells was assessed by flow cytometry and/or immunohistochemistry. Chemotactic migration was assayed with Lsp1 KO and Lsp1 Tg T cells. Adoptive transfer of Lsp1 KO or Lsp1 Tg T cells was performed in B16 melanoma-challenged Rag1 KO mice.Results Lsp1 KO mice showed decreased growth of B16 melanoma and increased infiltration of T cells in the tumor mass, which were completely reversed in T cell-specific Lsp1 Tg mice. Lsp1 KO CD8+ T cells also exhibited elevated migratory capacity in response to CXCL9 and CXCL10, whereas Lsp1 Tg CD8+ T cells did the opposite. LSP1 expression was increased in tumor-infiltrating T cells and could be induced by T cell receptor activation. Intriguingly, gene expression profiling of Lsp1 KO T cells suggested enhanced cytotoxicity. Indeed, expression of IFN-γ and TNF-α was increased in tumor-infiltrating CD4+ and CD8+ T cells of Lsp1 KO mice, while it was markedly reduced in those of Lsp1 Tg mice. Adoptive transfer of Lsp1 KO T cells to Rag1 KO mice was more effective in suppressing melanoma growth than transfer of Lsp1 Tg T cells. Of note, when treated with antiprogrammed cell death protein 1 (PD-1) antibody, inhibition of melanoma growth was more pronounced in Lsp1 KO mice than in Lsp1-sufficient mice, suggesting that Lsp1 depletion additively increases the antitumor effects of anti-PD-1 antibody.Conclusions LSP1 in T cells regulates the growth of B16 melanoma in mice, possibly by affecting migration and infiltration of T cells into the tumor and by modulating production of antitumor effector cytokines by CD8+ T cells. These findings provide evidence that LSP1 can be a target to improve the efficacy of T cell-based immunotherapy