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The combined actions of NK and T lymphocytes are necessary to reject an EGFP+ mesenchymal tumor through mechanisms dependent on NKG2D and IFNγ
Author(s) -
Arina Ainhoa,
Murillo Oihana,
HervásStubbs Sandra,
Azpilikueta Arantza,
Dubrot Juan,
Tirapu Iñigo,
Huarte Eduardo,
Alfaro Carlos,
PérezGracia Jose L.,
GonzálezAseguinolaza Gloria,
Sarobe Pablo,
Lasarte Juan J.,
Jamieson Amanda,
Prieto Jesús,
Raulet David H.,
Melero Ignacio
Publication year - 2007
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.22795
Subject(s) - nkg2d , biology , cancer research , immune system , cd8 , cytotoxic t cell , immunotherapy , mesenchymal stem cell , immunology , microbiology and biotechnology , in vitro , biochemistry
Better understanding of the mechanisms that mediate spontaneous immune rejections ought to be important in the quest for improvements in immunotherapy of cancer. A set of intraperitoneal tumors of mesenchymal origin that had been chemically induced in ubiquitously expressing EGFP transgenic mice provided a model in which both T and NK cells were absolutely required for tumor rejection. Tumor cells were traceable because of being fluorescent and readily grafted in RAG1 −/− immunodeficient mice, whereas they were rejected in a majority of syngeneic C57BL/6 and EGFP‐transgenic mice. Tumor‐cell clones with the highest EGFP expression tended to be rejected, but a direct involvement of EGFP as the antigen recognized for the immune rejections was ruled out. Rejections were absolutely dependent on NK cells as well as on CD4 + and CD8 + T lymphocytes according to selective depletion studies. Furthermore, CD8 + and CD4 + T lymphocytes as well as NK cells were detected in the inflammatory infiltrate that mediates tumor rejection along with some DC. The effects of IFNγ, produced at the tumor site by T and NK lymphocytes, were only required at the malignant cell level and were necessary for tumor eradication. NK recognition of tumor cells was mediated by the NKG2D‐activating receptor and blocking its function in vivo partially interfered with rejection. Therefore, complete rejection of these mesenchymal tumors requires a concerted set of activities including direct tumor‐cell destruction and IFNγ production that are mediated by both NK and T cells. © 2007 Wiley‐Liss, Inc.