Cancer Immunology, Immunotherapy

, Volume 61, Issue 2, pp 239–247

Immunological monitoring of the tumor immunoenvironment for clinical trials

  • Anatoli M. Malyguine
  • Susan L. Strobl
  • Michael R. Shurin
Focussed Research Review

DOI: 10.1007/s00262-011-1148-6

Cite this article as:
Malyguine, A.M., Strobl, S.L. & Shurin, M.R. Cancer Immunol Immunother (2012) 61: 239. doi:10.1007/s00262-011-1148-6

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.

Keywords

ImmunomonitoringVaccine clinical trialsTumor immunoenvironmentLeukocytesCITIM2011

Copyright information

© Springer-Verlag (outside the USA) 2011

Authors and Affiliations

  • Anatoli M. Malyguine
    • 1
  • Susan L. Strobl
    • 1
  • Michael R. Shurin
    • 2
  1. 1.Laboratory of Cell-Mediated ImmunitySAIC-Frederick, Inc.FrederickUSA
  2. 2.Department of Pathology, Division of Clinical ImmunopathologyUniversity of Pittsburgh Medical CenterPittsburghUSA