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High immunosuppressive burden in cancer patients: a major hurdle for cancer immunotherapy

  • Focussed Research Review
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

A bottleneck for immunotherapy of cancer is the immunosuppressive microenvironment in which the tumor cells are located. Regardless of the fact that large numbers of tumor-specific T cells can be generated in patients by active immunization or adoptive transfer, these T cells do not readily translate to tumor cell killing in vivo. The immune regulatory mechanism that prevents autoimmunity may be harnessed by tumor cells for the evasion of immune destruction. Regulatory T cells, myeloid-derived suppressor cells, inhibitory cytokines and immune checkpoint receptors are the major components of the immune system acting in concert with causing the subversion of anti-tumor immunity in the tumor microenvironment. This redundant immunosuppressive network may pose an impediment to efficacious immunotherapy, thus facilitating tumor progression. Cancer progression clearly documents the failure of immune control over relentless growth of tumor cells. Detailed knowledge of each of these factors responsible for creating an immunosuppressive shield to protect tumor cells from immune destruction is essential for the development of novel immune-based therapeutic interventions of cancer. Multipronged targeted depletion of these suppressor cells may restore production of granzyme B by CD8+ T cells and increase the number of IFN-γ-producing CD4+ T cells.

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Abbreviations

AFP:

Alpha-fetoprotein

Arg-1:

Arginase-1

CCR4:

Chemokine receptor type-4

COX2:

Cyclooxygenase-2

CRC:

Colorectal cancer

GARP:

Glycoprotein A repetition predominant

GPC-3:

Glypican-3

HCC:

Hepatocellular carcinoma

MAGE-A:

Melanoma antigen-A

mTOR:

Mammalian target of rapamycin

NO:

Nitric oxide

NY-ESO-1:

New York esophageal squamous cell cancer-1

PDE-5:

Phosphodiesterase-5

PKC:

Protein kinase C

ROS:

Reactive oxygen species

TAM:

Tumor-associated macrophages

Th1:

T helper 1

Tregs:

Regulatory T cells

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Acknowledgments

This research in the Thanavala Lab was supported in part through discretionary funds available to Dr. Thanavala. We gratefully acknowledge Dr. Paul Wallace and Earl Timm for their help in designing flow cytometry experiments. The patient samples were obtained through the Roswell Park Cancer Institute Data Bank and Biorepository which is a Cancer Center Support Grant (CCSG) Shared Resource supported by National Institute of Health P30 CA016056-27.

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Authors and Affiliations

  1. Department of Immunology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA

    Suresh Gopi Kalathil & Yasmin Thanavala

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  1. Suresh Gopi Kalathil
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  2. Yasmin Thanavala
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Correspondence to Yasmin Thanavala.

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None of the authors have any conflict of interest.

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This paper is a Focussed Research Review based on a presentation given at the Fourth International Conference on Cancer Immunotherapy and Immunomonitoring (CITIM 2015), held in Ljubljana, Slovenia, 27th–30th April 2015. It is part of a series of Focussed Research Reviews and meeting report in Cancer Immunology, Immunotherapy.

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Kalathil, S.G., Thanavala, Y. High immunosuppressive burden in cancer patients: a major hurdle for cancer immunotherapy. Cancer Immunol Immunother 65, 813–819 (2016). https://doi.org/10.1007/s00262-016-1810-0

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