TGF-β-dependent lymphoid tissue residency of stem-like T cells limits response to tumor vaccine

• DOI: 10.1038/s41467-022-33768-x
• Publication Date: 2022-10-13T11:03:20Z
• Authors: Guo Li; Saranya Srinivasan; Liwen Wang; Chaoyu Ma; Kai Guo; Wenhao Xiao; Wei Liao; Shruti Mishra; Xin Zhang; Yuanzheng Qiu; Qianjin Lu; Yong Liu; Nu Zhang
• Keywords: AIDS Vaccines; 0303 health sciences; Lymphoid Tissue; Science; Q; SAIDS Vaccines; CD8-Positive T-Lymphocytes; Cancer Vaccines; Article; 3. Good health; Mice; Epitopes; 03 medical and health sciences; Antigens, Neoplasm; Influenza Vaccines; Transforming Growth Factor beta; BCG Vaccine; Respiratory Syncytial Virus Vaccines; Animals; Papillomavirus Vaccines; Immunologic Memory; Melanoma; Diphtheria-Tetanus-Pertussis Vaccine; Measles-Mumps-Rubella Vaccine

TGF-β signaling is necessary for CD8+ T cell differentiation into tissue resident memory cells (TRM). Although higher frequency of TRM in the tumor microenvironment associated with better prognosis, TGF-β-blockade typically improves rather than worsens outcomes. Here we show that a mouse melanoma model, tumor-draining lymph nodes (TDLN) tumors themselves, stem-like differentiate TRMs and antigen dependent manner. Following vaccination against melanoma-specific epitope, most tumour-specific are maintained state, but proportion lost status CX3CR1+ effector TDLN, which subsequently migrating tumours. Disruption changes dynamics these developmental processes, net result improving migration In summary, TDLN transiently switch from TGF-β-dependent program to an anti-tumor migratory development upon vaccination, transition can be facilitated by targeted blockade.