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Review
. 2016 Sep 2;4(3):29.
doi: 10.3390/vaccines4030029.

Monitoring of the Immune Dysfunction in Cancer Patients

Saskia J A M Santegoets  1 , Marij J P Welters  2 , Sjoerd H van der Burg  3
Affiliations
Review

Monitoring of the Immune Dysfunction in Cancer Patients

Saskia J A M Santegoets et al. Vaccines (Basel). .

Abstract

Immunotherapy shows promising clinical results in patients with different types of cancer, but its full potential is not reached due to immune dysfunction as a result of several suppressive mechanisms that play a role in cancer development and progression. Monitoring of immune dysfunction is a prerequisite for the development of strategies aiming to alleviate cancer-induced immune suppression. At this point, the level at which immune dysfunction occurs has to be established, the underlying mechanism(s) need to be known, as well as the techniques to assess this. While it is relatively easy to measure general signs of immune suppression, it turns out that accurate monitoring of the frequency and function of immune-suppressive cells is still difficult. A lack of truly specific markers, the phenotypic complexity among suppressive cells of the same lineage, but potentially with different functions and functional assays that may not cover every mechanistic aspect of immune suppression are among the reasons complicating proper assessments. Technical innovations in flow and mass cytometry will allow for more complete sets of markers to precisely determine phenotype and associated function. There is, however, a clear need for functional assays that recapitulate more of the mechanisms employed to suppress the immune system.

Keywords: anti-tumor response; functional assays; immune dysfunction; immunomonitoring; immunosuppression; myeloid-derived suppressor cells; phenotyping; regulatory T cells; tumor-associated macrophages; tumor-associated neutrophils.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Overview and measurement of the different levels of immune dysfunction present in cancer patients. Immune dysfunction can be analyzed through measuring general signs of immune suppression in the blood (top left) and through measuring the frequency and function of suppressor cells in the blood and tumor tissue (bottom left). The different parameters that can be measured studying these levels of immune dysfunction are depicted (middle), as well as the techniques that can be used (right). Abbreviations used: APC: antigen-presenting cell; Arg1: arginase 1; CBC: complete blood count; CMV: cytomegalovirus; DBC: differential blood count; EBV: Epstein-Barr virus; GARP: glycoprotein A repetitions predominant; ICS: intracellular cytokine staining; IDO: indoleamine-2,3-deoxigenase; IHC: immunohistochemistry; iNOS: inducible nitric oxide synthase; MDSC: myeloid-derived suppressor cells; MLR: mixed lymphocyte reaction; NK: natural killer; NO: nitric oxide; PBMC: peripheral blood mononuclear cells; PHA: phytohemagglutinin; qPCR: quantitative polymerase chain reaction; ROS: reactive oxygen species; SEB: staphylococcal enterotoxin B; TAA: tumor-associated antigen; TAM: tumor-associated macrophages; TAN: tumor-associated neutrophils; TGF-β: transforming growth factor receptor-β; Treg: regulatory T cells.
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