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Background: Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer. PDAC's poor prognosis and resistance to immunotherapy are attributed in part to its dense, fibrotic tumor microenvironment (TME), which is known to inhibit immune cell infiltration. We recently demonstrated that PDAC patients with higher natural killer (NK) cell content and activation have better survival rates. However, NK cell interactions in the PDAC TME have yet to be deeply studied. We show here that NK cells are present and active in the human PDAC TME. Methods: We used imaging mass cytometry (IMC) to assess NK cell content, function, and spatial localization in human PDAC samples. Then, we used CellChat, a tool to infer ligand-receptor interactions, on a human PDAC scRNAseq dataset to further define NK cell interactions in PDAC. Results: Spatial analyses showed for the first time that active NK cells are present in the PDAC TME, and both associate and interact with malignant epithelial cell ducts. We also found that fibroblast-rich, desmoplastic regions limit NK cell infiltration in the PDAC TME. CellChat analysis identified that the CD44 receptor on NK cells interacts with PDAC extracellular matrix (ECM) components such as collagen, fibronectin and laminin expressed by fibroblasts and malignant epithelial cells. This led us to hypothesize that these interactions play roles in regulating NK cell motility in desmoplastic PDAC TMEs. Using 2D and 3D in vitro assays, we found that CD44 neutralization significantly increased NK cell invasion through matrix. Conclusions: Targeting ECM-immune cell interactions may increase NK cell invasion into the PDAC TME.
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AIM: To explore the life experiences of women with interstitial cystitis. DESIGN: A qualitative phenomenological study. METHODS: Fifteen women with interstitial cystitis were recruited from a regional hospital in Taiwan using purposive sampling. Data were collected via one-on-one semistructured interviews and analysed using the Colaizzi's method. Rigorous testing was conducted to identify the themes and subthemes. RESULTS: Four major themes were identified: torment, restriction, acceptance and empowerment. These themes reflect the life experiences of women with interstitial cystitis. They endured unrelenting physical and psychological distress and loneliness, experienced obstacles and limitations in daily living because of their symptoms, accepted reality and considered their symptoms as a part of everyday life and developed coping skills for the disease. CONCLUSION: Medical care, psychological support and emotional venting are crucial for women with interstitial cystitis. Despite living a life full of frustrations and suffering caused by the unpredictable and unrelenting nature of interstitial cystitis, through external support and intrinsic positive cognitive reconstruction, women with interstitial cystitis gradually accepted that they were ill. They adapted to their situation, developed a suitable lifestyle and pace and ultimately achieved stable coexistence with the disease. IMPLICATIONS FOR THE PROFESSION AND PATIENT CARE: Although women with interstitial cystitis are affected by an incurable disease, through adequate assistance and reconstruction of perception, they can develop coping skills and stably coexist with their disease. There is a delicate dynamic balance between their lives and disease. IMPACT: This study may help clinicians to understand patients' life experiences and provide suitable care. This may improve the quality of care provided to women with interstitial cystitis and help them adapt to their disease, thereby improving their life satisfaction. REPORTING METHOD: This study was reported according to the COREQ checklist. PATIENT OR PUBLIC CONTRIBUTION: Women with interstitial cystitis contributed to the study data.
