Publicação
Tumor-Infiltrating Natural Killer Cell Characterization in Pancreatic Ductal Adenocarcinoma
| 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 |
| _version_ | 1866752610228240384 |
|---|---|
| author | Maia, Andreia |
| author2 | 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 |
| author2_role | author author author author author author author author author author |
| author_facet | Maia, Andreia 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 |
| author_role | author |
| contributor_name_str_mv | NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) MDPI - Multidisciplinary Digital Publishing Institute RUN |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Maia, Andreia\"},{\"Person.name\":\"Calá, Hasti\"},{\"Person.name\":\"de Sousa, Eric\"},{\"Person.name\":\"Lérias, Joana R.\"},{\"Person.name\":\"Gorgulho, Carolina M.\"},{\"Person.name\":\"António, Patrícia A.\"},{\"Person.name\":\"Kamiki, Jéssica\"},{\"Person.name\":\"Ligeiro, Dário\"},{\"Person.name\":\"Borrego, Luis M.\"},{\"Person.name\":\"Maeurer, Markus\"},{\"Person.name\":\"Castillo-Martin, Mireia\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) MDPI - Multidisciplinary Digital Publishing Institute RUN |
| datacite.creators.creator.creatorName.fl_str_mv | Maia, Andreia 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 |
| datacite.date.Accepted.fl_str_mv | 2026-05-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2026-05-22T15:07:01Z |
| datacite.date.embargoed.fl_str_mv | 2026-05-22T15:07:01Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | 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 |
| datacite.titles.title.fl_str_mv | Tumor-Infiltrating Natural Killer Cell Characterization in Pancreatic Ductal Adenocarcinoma |
| dc.contributor.none.fl_str_mv | NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) MDPI - Multidisciplinary Digital Publishing Institute RUN |
| dc.creator.none.fl_str_mv | Maia, Andreia 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 |
| dc.date.Accepted.fl_str_mv | 2026-05-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2026-05-22T15:07:01Z |
| dc.date.embargoed.fl_str_mv | 2026-05-22T15:07:01Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10362/203332 |
| dc.language.none.fl_str_mv | eng |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | 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 |
| dc.title.fl_str_mv | Tumor-Infiltrating Natural Killer Cell Characterization in Pancreatic Ductal Adenocarcinoma |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | 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. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://run.unl.pt/bitstreams/bead53bd-0292-4d20-9f11-0650f9f04126/download |
| id | run_ef82dd287d0da2c2f38c45a8b19a04ca |
| identifier.url.fl_str_mv | http://hdl.handle.net/10362/203332 |
| instacron_str | unl |
| institution | Universidade Nova de Lisboa |
| instname_str | Universidade Nova de Lisboa |
| language | eng |
| network_acronym_str | run |
| network_name_str | Repositório Institucional da UNL |
| oai_identifier_str | oai:run.unl.pt:10362/203332 |
| organization_str_mv | urn:organizationAcronym:unl |
| person_str_mv | Maia, Andreia 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 |
| publishDate | 2026 |
| reponame_str | Repositório Institucional da UNL |
| repository_id_str | urn:repositoryAcronym:run |
| service_str_mv | urn:repositoryAcronym:run |
| spelling | engenPancreatic 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.application/pdfenTumor-Infiltrating Natural Killer Cell Characterization in Pancreatic Ductal AdenocarcinomaMaia, AndreiaCalá, Hastide Sousa, EricLérias, Joana R.Gorgulho, Carolina M.António, Patrícia A.Kamiki, JéssicaLigeiro, DárioBorrego, Luis M.Maeurer, MarkusCastillo-Martin, MireiaNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)MDPI - Multidisciplinary Digital Publishing InstituteHostingInstitutionOrganizationalRUNe-mailmailto:run@unl.ptrun@unl.ptISSNIsPartOf2073-4409URNIsPartOfPURE: 163205937URNIsPartOfPURE UUID: ede5fe26-6f1e-4dcd-870d-3e1a42cb0d25URNIsPartOfScopus: 105038401277URNIsPartOfORCID: /0000-0003-4708-438X/work/215513568DOIIsPartOf10.3390/cells150907972026-05-22T15:07:01Z2026-052026-05-01T00:00:00ZHandlehttp://hdl.handle.net/10362/203332http://purl.org/coar/access_right/c_abf2open accessadoptive cell therapynatural killer cellsNK-TILpancreatic ductal adenocarcinomasolid tumoursTIL therapytumor-infiltrating lymphocytesGeneral Biochemistry,Genetics and Molecular BiologySDG 3 - Good Health and Well-being3656918 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://run.unl.pt/bitstreams/bead53bd-0292-4d20-9f11-0650f9f04126/download |
| spellingShingle | Tumor-Infiltrating Natural Killer Cell Characterization in Pancreatic Ductal Adenocarcinoma Maia, Andreia 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 |
| status | SINGLETON |
| subject.fl_str_mv | 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 |
| title | Tumor-Infiltrating Natural Killer Cell Characterization in Pancreatic Ductal Adenocarcinoma |
| title_full | Tumor-Infiltrating Natural Killer Cell Characterization in Pancreatic Ductal Adenocarcinoma |
| title_fullStr | Tumor-Infiltrating Natural Killer Cell Characterization in Pancreatic Ductal Adenocarcinoma |
| title_full_unstemmed | Tumor-Infiltrating Natural Killer Cell Characterization in Pancreatic Ductal Adenocarcinoma |
| title_short | Tumor-Infiltrating Natural Killer Cell Characterization in Pancreatic Ductal Adenocarcinoma |
| title_sort | Tumor-Infiltrating Natural Killer Cell Characterization in Pancreatic Ductal Adenocarcinoma |
| topic | 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 |
| topic_facet | 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 |
| url | http://hdl.handle.net/10362/203332 |
| visible | 1 |