RESUMEN
Natural killer (NK) cells are an important component of anti-cancer immunity, and their activity is regulated by an array of activating and inhibitory receptors. In mice, the inhibitory NKR-P1B receptor is expressed in NK cells and recognizes the C-type lectin-related protein-b (Clr-b) ligand. NKR-P1B:Clr-b interactions represent a 'missing-self' recognition system to monitor cellular levels of Clr-b on healthy and diseased cells. Here, we report an important role for NKR-P1B:Clr-b interactions in tumor immunosurveillance in MMTV-PyVT mice, which develop spontaneous mammary tumors. MMTV-PyVT mice on NKR-P1B-deficient genetic background developed mammary tumors earlier than on wild-type (WT) background. A greater proportion of tumor-infiltrating NK cells downregulate expression of the transcription factor Eomesodermin (EOMES) in NKR-P1B-deficient mice compared to WT mice. Tumor-infiltrating NK cells also downregulated CD49b expression but gain CD49a expression and exhibit effector functions, such as granzyme B upregulation and proliferation in mammary tumors. However, unlike the EOMES+ NK cells, the EOMESâ NK cell subset is unable to respond to further in vitro stimulation and exhibits phenotypic alterations associated with immune dysfunction. These alterations included increased expression of PD-1, LAG-3, and TIGIT and decreased expression of NKp46, Ly49C/I, CD11b, and KLRG-1. Furthermore, tumor-infiltrating NKR-P1B-deficient NK cells exhibited an elevated dysfunctional immune phenotype compared to WT NK cells. These findings demonstrate that the NKR-P1B receptor plays an important role in mammary tumor surveillance by regulating anti-cancer immune responses and functional homeostasis in NK cells.
Asunto(s)
Vigilancia Inmunológica , Células Asesinas Naturales , Subfamilia B de Receptores Similares a Lectina de Células NK , Animales , Ratones , Células Asesinas Naturales/metabolismo , Ligandos , Fenotipo , Neoplasias de la Mama/inmunologíaRESUMEN
Despite their essential role in Canadian agriculture, migrant workers face numerous healthcare barriers. There is a knowledge gap regarding the healthcare experiences of migrant workers with critical illness in the Windsor-Essex region. Our objective was to collect information on the experiences of migrant workers experiencing a critical illness at Windsor Regional Hospital (WRH) between 31 December 2011 and 31 December 2021. We conducted a retrospective chart review and interviews with migrant workers. We identified 14 migrant workers who presented to WRH with a critical illness over these 10 years. Despite occasional barriers regarding access to care, the migrant workers received an appropriate standard of care in Canada. Five of the fourteen patients identified were repatriated to their home countries. The migrant worker patients interviewed expressed satisfaction with the care they received in Canada but identified repatriation as a specific concern to receiving continuity of care. The health and financial burden imposed by critical illness on migrant workers and their employers makes critically ill workers vulnerable to medical repatriation as a unique social determinant of health. Considering the critical role of migrant workers in Canada's food security, policy changes should be considered to ensure critically ill workers are able to remain until recovery.