Spatial distribution and activation changes of T cells in pancreatic tumors according to KRAS mutation subtype.

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Tác giả: Dong-Jun Bae, Jung Kyoon Choi, Ji Hye Jeong, Eunsung Jun, Chong Jai Kim, Jinju Kim, Sang-Yeob Kim, Song Cheol Kim, Eun-Young Koh, Jae Soon Park, Dakyum Shin, Young Hoon Sung

Ngôn ngữ: eng

Ký hiệu phân loại: 785.13 *Trios

Thông tin xuất bản: Ireland : Cancer letters , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 718948

To enhance immunotherapy efficacy in pancreatic cancer, it is crucial to characterize its immune landscape and identify key factors driving immune alterations. To achieve this, we quantitatively analyzed the immune microenvironment using multiplex immunohistochemistry, assessing the spatial relationships between immune and tumor cells to correlate with patient survival rates and oncological factors. Additionally, through Whole Exome Sequencing analysis based on public data, we explored genetic mutations that could drive these compositions. Finally, we validated T cell (Tc) migration mechanisms using patient-derived tumor organoids with induced KRAS mutation subtypes. Through this approach, we obtained the following meaningful results. First, immune cells in pancreatic cancer are denser in stromal regions than near tumor cells, with higher Tc distribution linked to increased patient survival rates. Second, the distance between tumor and Tc was within 100 μm, with higher Tc density found within 15-30 μm of the tumor cells. Third, while increasing CAF levels correspond to higher Tc density, higher ECM density tends to decrease Tc presence. Fourth, compared to KRAS G12D, KRAS G12V mutation increases various immune cells, notably Tc, which is closely linked to a dramatic rise in vascular cells. Finally, Tc migration was enhanced in tumor organoids with the G12V mutation, attributed to a reduction in the secretion of immunosuppressive cytokines. Our results indicate that KRAS mutation subtypes influence immune cell composition and function in the pancreatic cancer microenvironment, leading to varied immunotherapy responses. This underscores the need for personalized immune therapeutics and research models specific to KRAS mutations.
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