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@ARTICLE{Roberti:298574,
      author       = {M. P. Roberti$^*$ and P. Charoentong$^*$ and Y. Lyu and M.
                      Meyer$^*$ and S. Eichmüller$^*$ and P. Schmidt$^*$ and F.
                      Momburg$^*$ and M. Cetin$^*$ and F. Hartmann$^*$ and N.
                      Valous$^*$ and A. Stenzinger and L. Michel$^*$ and P.
                      Lichter$^*$ and A. Schneeweiss$^*$ and V. Thewes$^*$ and C.
                      Fremd$^*$ and I. Zörnig$^*$ and D. Jäger$^*$},
      title        = {{I}solation of a tumor neoantigen specific {CD}8+ {TCR}
                      from a skin biopsy of a vaccination site.},
      journal      = {OncoImmunology},
      volume       = {14},
      number       = {1},
      issn         = {2162-4011},
      address      = {Abingdon},
      publisher    = {Taylor $\&$ Franics},
      reportid     = {DKFZ-2025-00291},
      pages        = {2457793},
      year         = {2025},
      note         = {#EA:D120#LA:D120#},
      abstract     = {T cells that recognize tumor-specific mutations are crucial
                      for cancer immunosurveillance and in adoptive transfer of
                      TILs or transgenic-TCR T cell products. However, their
                      challenging identification and isolation limits their use in
                      clinical practice. Therefore, novel approaches to isolate
                      tumor-specific T cells are needed. Here, we report the
                      isolation of neoantigen-specific CD8+ T cells from a
                      vaccination site of a metastatic breast cancer patient who
                      received a personalized vaccine. Based on the somatic
                      mutations, potential MHC binding epitopes were predicted, of
                      which 17 were selected to generate a peptide vaccine.
                      Cutaneous biopsies were processed after the fifth
                      vaccination cycle to obtain infiltrating lymphocytes from
                      the vaccination site (VILs). IFNγ ELISpot revealed
                      reactivity to four peptides used in the vaccine. Reactive T
                      cells from VILs were non-overlapping with those detected in
                      the blood and the tumor-microenvironment. ScTCR Seq analysis
                      revealed the presence of a clonotype in VILs that further
                      expanded after a round of in vitro stimulation and validated
                      to be specific against a private mutation, namely
                      NCOR1L1475R, presented in the context of HLA-B * 07:02, with
                      no reactivity to the wild-type peptide. Our study shows, for
                      the first time, that tumor mutation - specific T cells are
                      generated at high frequencies in the vaccination site and
                      can be isolated with standard methods for TCR screening. The
                      easy and safe accessibility of skin biopsies overcomes the
                      major hurdles of current TCR screening approaches and
                      present exciting opportunities for the development of
                      innovative immunotherapeutic strategies.},
      keywords     = {Humans / CD8-Positive T-Lymphocytes: immunology / Antigens,
                      Neoplasm: immunology / Female / Cancer Vaccines: immunology
                      / Cancer Vaccines: administration $\&$ dosage / Skin:
                      pathology / Skin: immunology / Biopsy / Breast Neoplasms:
                      immunology / Breast Neoplasms: pathology / Receptors,
                      Antigen, T-Cell: immunology / Receptors, Antigen, T-Cell:
                      genetics / Vaccination / Lymphocytes, Tumor-Infiltrating:
                      immunology / Mutation / Breast cancer (Other) / T cell
                      receptor engineered T cells (Other) / TILs (Other) / VILs
                      (Other) / adoptive T cell therapy (Other) / neoantigen
                      (Other) / peptide vaccine (Other) / vaccination site
                      infiltrating lymphocytes (Other) / Antigens, Neoplasm (NLM
                      Chemicals) / Cancer Vaccines (NLM Chemicals) / Receptors,
                      Antigen, T-Cell (NLM Chemicals)},
      cin          = {D120 / D210 / D260 / HD01 / B060},
      ddc          = {610},
      cid          = {I:(DE-He78)D120-20160331 / I:(DE-He78)D210-20160331 /
                      I:(DE-He78)D260-20160331 / I:(DE-He78)HD01-20160331 /
                      I:(DE-He78)B060-20160331},
      pnm          = {314 - Immunologie und Krebs (POF4-314)},
      pid          = {G:(DE-HGF)POF4-314},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39902862},
      pmc          = {pmc:PMC11796541},
      doi          = {10.1080/2162402X.2025.2457793},
      url          = {https://inrepo02.dkfz.de/record/298574},
}