Suppression of Antitumor Immunity by Stromal Cells Expressing Fibroblast Activation Protein–α

@article{Kraman2010SuppressionOA,
  title={Suppression of Antitumor Immunity by Stromal Cells Expressing Fibroblast Activation Protein–$\alpha$},
  author={Matthew Kraman and Paul J. Bambrough and James N Arnold and Edward W. Roberts and Lukasz Magiera and James O. Jones and Aarthi Gopinathan and David A. Tuveson and Douglas T. Fearon},
  journal={Science},
  year={2010},
  volume={330},
  pages={827 - 830}
}
The stromal microenvironment of tumors, which is a mixture of hematopoietic and mesenchymal cells, suppresses immune control of tumor growth. [] Key Result Depletion of FAP-expressing cells, which made up only 2% of all tumor cells in established Lewis lung carcinomas, caused rapid hypoxic necrosis of both cancer and stromal cells in immunogenic tumors by a process involving interferon-γ and tumor necrosis factor-α.

Disruption of Anti-tumor T Cell Responses by Cancer-Associated Fibroblasts

Recent advances in the understanding the tumor micro-environment reveals potential new ways for attacking tumor cells, especially T cells.

A whole-cell tumor vaccine modified to express fibroblast activation protein induces antitumor immunity against both tumor cells and cancer-associated fibroblasts

It is indicated that the FAP-modified whole-cell tumor vaccine induced strong antitumor immunity against both tumor cells and CAFs and reversed the immunosuppressive effects of tumors by decreasing the recruitment of immunOSuppressive cells and enhancing the recruitmentof effector T cells.

Immunotherapy of tumor with vaccine based on basic fibroblast growth factor-activated fibroblasts

PurposeCancer-associated fibroblasts play a key role in tumor progression. It is conceivable that the breaking of immune tolerance of “self-antigens” associated with tumor cells and tumor stromal is

Mesenchymal stromal cells inhibit murine syngeneic anti-tumor immune responses by attenuating inflammation and reorganizing the tumor microenvironment

MSCs in the tumor environment reduce the efficacy of immunotherapy by creating a functional and anatomic barrier that impairs inflammation, T cell priming and expansion, and T cell function—including recruitment of effector cells.

Antitumor immunity targeting fibroblast activation protein-α in a mouse Lewis lung carcinoma model

The results of the present study suggested that FAP-α, which is preferentially expressed in CAFs, may be considered as a potential target for killing or destroying CAFs within the tumor stromal microenvironment, and may be exploited to develop immunogenic tumor vaccines.

Viral vector-mediated reprogramming of the fibroblastic tumor stroma sustains curative melanoma treatment

It is shown that intratumoral treatment of mice with a recombinant lymphocytic choriomeningitis virus-based vaccine vector resulted in T cell-dependent long-term control of melanomas and reprogramming of FSCs by a self-antigen-expressing viral vector in the TME is critical for curative melanoma treatment.

Anti-tumor effects of DNA vaccine targeting human fibroblast activation protein α by producing specific immune responses and altering tumor microenvironment in the 4T1 murine breast cancer model

A DNA vaccine targeting human FAPα may be an attractive and effective cancer immunotherapy strategy and reduce 4T1 tumor growth through producing FAP α-specific cytotoxic T lymphocyte responses which could kill CAFs.

The Carcinoma-Associated Fibroblast Expressing Fibroblast Activation Protein and Escape from Immune Surveillance

  • D. Fearon
  • Biology, Medicine
    Cancer Immunology Research
  • 2014
The conditional depletion of the FAP+ CAF permits immune control not only of an artificial, transplanted tumor, but also of an autochthonous model of pancreatic ductal adenocarcinoma that replicates the molecular, histologic, clinical, and immunologic characteristics of the human disease.

Immunization of stromal cell targeting fibroblast activation protein providing immunotherapy to breast cancer mouse model

Results implicated that immunization with FAP+ stromal cells led to the disruption of the tumor microenvironment and may provide a novel strategy for immunotherapy of a broad range of cancer.
...

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