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Immunological monitoring of the tumor immunoenvironment for clinical trials

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

Abstract

Monitoring of immunotherapeutic clinical trials has undergone a considerable change in the last decade resulting in a general agreement that immune monitoring should guide the development of cancer vaccines. The emphasis on immune cell functions and quantitation of antigen-specific T cells have been playing a major role in the attempts to establish meaningful correlations between therapy-induced alterations in immune responses and clinical endpoints. However, one significant unresolved issue in modern immunotherapy is that when a tumor-specific cellular immune response is observed following the course of immunotherapy, it does not always lead to clinically proven cancer regression. This disappointing lack of a correlation between the tumor-specific cytotoxic immune responses and the clinical efficacy of immunotherapy may be explained, among other reasons, by the notion that the analysis of any single immunological parameter is not sufficient to provide clinically feasible information about the complex interactions between different cell subsets in the peripheral blood and immune, tumor, and stromal cells in the tumor milieu. By contrast, a systemic approach is required for improving the quality of a serial monitoring to ensure that it adequately and reliably measures potential changes induced in patients by administered vaccines or immunomodulators. Comprehensive evaluation of the balance between the immunostimulatory and immunosuppressive compartments of the immune system could be critical for a better understanding of how a given immunotherapy works or does not work in a particular clinical trial. New approaches to characterize tumor-infiltrating leukocytes, their phenotypic, biochemical, and genetic characteristics within the tumor microenvironment need to be developed and validated and should complement current monitoring techniques. These immune-monitoring assays for the local tumor immunoenvironment should be developed, validated, and standardized for reliability and consistency in order to establish the overall performance standards.

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Acknowledgments

This project was supported by NIH RO1 CA154369 grant (to M.R.S.). This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract no. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Laboratory of Cell-Mediated Immunity, SAIC-Frederick, Inc., P.O. Box B, Frederick, MD, 21702, USA

    Anatoli M. Malyguine & Susan L. Strobl

  2. Department of Pathology, Division of Clinical Immunopathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    Michael R. Shurin

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  1. Anatoli M. Malyguine
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  2. Susan L. Strobl
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  3. Michael R. Shurin
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Correspondence to Anatoli M. Malyguine.

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This article is a Focussed Research Review based on a presentation given at the Second International Conference on Cancer Immunotherapy and Immunomonitoring (CITIM 2011) held in Budapest, Hungary, May 2 to 5, 2011. It is part of a CII series of Focussed Research Reviews and meeting report.

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Malyguine, A.M., Strobl, S.L. & Shurin, M.R. Immunological monitoring of the tumor immunoenvironment for clinical trials. Cancer Immunol Immunother 61, 239–247 (2012). https://doi.org/10.1007/s00262-011-1148-6

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