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Immunotherapy of Metastatic Colorectal Cancer: Prevailing Challenges and New Perspectives

Abstract

Patients with recurring or metastatic colorectal cancer (mCRC) have strikingly low long-term survival, while conventional treatments such as chemotherapeutic intervention and radiation therapy marginally improve longevity. Although many factors involving immunosurveillance and immunosuppression were recently validated as important for patient prognosis and care, a multitude of experimental immunotherapies designed to combat unresectable mCRC have, in few cases, successfully mobilized anti-tumor immune cells against malignancies nor conclusively or consistently granted protection, complete remission, and/or stable disease from immunotherapy, benefitting less than 10 % of those receiving therapy. After decades of progress, however, new insights into the mechanisms of immunosuppression, tolerance, and mutation profiling established novel therapies that circumvent these immunological barriers. This review underlines the most exciting methods to date that manipulate immune cells to curb mCRC, including adoptive cell therapy, dendritic cell vaccines, and checkpoint inhibitor antibodies, hinting at effective and enduring protection against disease progression and undetected micrometastases.

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Grant Funding

This work was supported by grants R01 CA72851, CA181572 and U01 CA187956 from the National Cancer Institute, National Institutes of Health, pilot grant from Charles A Sammons Cancer Center, and funds from the Baylor Research Institute to AG.

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Timothy J. Zumwalt and Ajay Goel declare that they have no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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Correspondence to Ajay Goel.

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This article is part of the Topical Collection on Therapeutic Approaches to Metastatic Colorectal Cancers

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Zumwalt, T.J., Goel, A. Immunotherapy of Metastatic Colorectal Cancer: Prevailing Challenges and New Perspectives. Curr Colorectal Cancer Rep 11, 125–140 (2015). https://doi.org/10.1007/s11888-015-0269-2

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Keywords

  • Metastatic colorectal cancer
  • T cell
  • Cytotoxic T lymphocyte
  • Helper T cell
  • Regulatory T cell
  • Immunotherapy
  • Dendritic cell
  • Macrophage
  • Myeloid-derived suppressor cell
  • Vaccine
  • Antibody therapy
  • Adoptive T cell therapy
  • Allogeneic stem cell transplant
  • Ipilimumab
  • CTLA-4
  • PD-1/L1
  • Immunosuppression
  • Immunosurveillance
  • Biomarker
  • Anti-tumor immunity
  • Adoptive immunotherapy