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TGF-ß-dependent lymphoid tissue residency of stem-like T cells limits response to tumor vaccine.
Li, Guo; Srinivasan, Saranya; Wang, Liwen; Ma, Chaoyu; Guo, Kai; Xiao, Wenhao; Liao, Wei; Mishra, Shruti; Zhang, Xin; Qiu, Yuanzheng; Lu, Qianjin; Liu, Yong; Zhang, Nu.
Afiliación
  • Li G; Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA.
  • Srinivasan S; Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China.
  • Wang L; Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
  • Ma C; Clinical Research Center for Laryngopharyngeal and Voice Disorders in Hunan Province, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
  • Guo K; Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA.
  • Xiao W; Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA.
  • Liao W; Department of Hematology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, China.
  • Mishra S; Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA.
  • Zhang X; Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China.
  • Qiu Y; Department of Medical Imaging, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, China.
  • Lu Q; Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China.
  • Liu Y; Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA.
  • Zhang N; Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
Nat Commun ; 13(1): 6043, 2022 10 13.
Article en En | MEDLINE | ID: mdl-36229613
TGF-ß signaling is necessary for CD8+ T cell differentiation into tissue resident memory T cells (TRM). Although higher frequency of CD8+ TRM cells in the tumor microenvironment is associated with better prognosis, TGF-ß-blockade typically improves rather than worsens outcomes. Here we show that in a mouse melanoma model, in the tumor-draining lymph nodes (TDLN) rather than in the tumors themselves, stem-like CD8+ T cells differentiate into TRMs in a TGF-ß and tumor antigen dependent manner. Following vaccination against a melanoma-specific epitope, most tumour-specific CD8+ T cells are maintained in a stem-like state, but a proportion of cells lost TRM status and differentiate into CX3CR1+ effector CD8+ T cells in the TDLN, which are subsequently migrating into the tumours. Disruption of TGF-ß signaling changes the dynamics of these developmental processes, with the net result of improving effector CD8+ T cell migration into the tumours. In summary, TDLN stem-like T cells transiently switch from a TGF-ß-dependent TRM differentiation program to an anti-tumor migratory effector development upon vaccination, which transition can be facilitated by targeted TGF-ß blockade.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vacunas contra la Influenza / Vacunas contra el SIDA / Vacunas contra el SIDAS / Vacunas contra el Cáncer / Vacunas contra Virus Sincitial Respiratorio / Vacunas contra Papillomavirus / Melanoma Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vacunas contra la Influenza / Vacunas contra el SIDA / Vacunas contra el SIDAS / Vacunas contra el Cáncer / Vacunas contra Virus Sincitial Respiratorio / Vacunas contra Papillomavirus / Melanoma Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido