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Tumor-Infiltrating Natural Killer Cell Characterization in Pancreatic Ductal Adenocarcinoma

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Resumo:Pancreatic ductal adenocarcinoma (PDAC) has high mortality rates, poor prognosis, and currently limited effective treatments. Natural killer (NK) cells from tumor-infiltrating lymphocytes (TIL) show promise for cancer treatment due to their ability to migrate to the tumor microenvironment (TME) and safe profile. However, expanding functional patient-derived NK cells remains challenging. Here, we cultured, expanded, and characterized TIL-NK cells isolated from central and peripheral tumor regions from PDAC. Ex vivo patient-derived PBMCs and TIL were cultured under IL-2, IL-15, and IL-12 stimulation. Phenotypical and functional NK cell characterization was assessed at the time of surgery and after 12 days of culture evaluating immunophenotype, expansion rate, and activation. A distinct distribution of NK cell infiltration was observed within the TME, with higher NK cell numbers in the periphery of the tumor compared to the central area. Most NK cells displayed a cytotoxic phenotype (CD56+ CD16+). Compared to PBMCs, TIL-NK cells expressed lower activation markers but superior tumor infiltration and expansion rates, particularly those isolated from the central regions. Notably, cytokine stimulation improved patient-derived NK cell activation and cytotoxic profile. This pilot study provides preliminary but critical insights regarding TIL-NK cells from PDAC patients, laying groundwork for developing NK cell-based immunotherapies for solid tumors.
Autores principais:Maia, Andreia
Outros Autores:Calá, Hasti; de Sousa, Eric; Lérias, Joana R.; Gorgulho, Carolina M.; António, Patrícia A.; Kamiki, Jéssica; Ligeiro, Dário; Borrego, Luis M.; Maeurer, Markus; Castillo-Martin, Mireia
Assunto:adoptive cell therapy natural killer cells NK-TIL pancreatic ductal adenocarcinoma solid tumours TIL therapy tumor-infiltrating lymphocytes General Biochemistry,Genetics and Molecular Biology SDG 3 - Good Health and Well-being
Ano:2026
País:Portugal
Tipo de documento:artigo
Tipo de acesso:acesso aberto
Instituição associada:Universidade Nova de Lisboa
Idioma:inglês
Origem:Repositório Institucional da UNL

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