Cancer and Metastasis Reviews

, Volume 26, Issue 3, pp 373–400

Inflammatory cell infiltration of tumors: Jekyll or Hyde

Authors

    • Laboratory of Transplantation Immunology, Department of Pathology and MicrobiologyUniversity of Nebraska Medical Center
  • Moses Donkor
    • Laboratory of Transplantation Immunology, Department of Pathology and MicrobiologyUniversity of Nebraska Medical Center
  • Eric Scholar
    • Department of Pharmacology and Experimental NeuroscienceUniversity of Nebraska Medical Center
Article

DOI: 10.1007/s10555-007-9072-0

Cite this article as:
Talmadge, J.E., Donkor, M. & Scholar, E. Cancer Metastasis Rev (2007) 26: 373. doi:10.1007/s10555-007-9072-0

Abstract

Inflammatory cell infiltration of tumors contributes either positively or negatively to tumor invasion, growth, metastasis, and patient outcomes, creating a Dr. Jekyll or Mr. Hyde conundrum when examining mechanisms of action. This is due to tumor heterogeneity and the diversity of the inflammatory cell phenotypes that infiltrate primary and metastatic lesions. Tumor infiltration by macrophages is generally associated with neoangiogenesis and negative outcomes, whereas dendritic cell (DC) infiltration is typically associated with a positive clinical outcome in association with their ability to present tumor antigens (Ags) and induce Ag-specific T cell responses. Myeloid-derived suppressor cells (MDSCs) also infiltrate tumors, inhibiting immune responses and facilitating tumor growth and metastasis. In contrast, T cell infiltration of tumors provides a positive prognostic surrogate, although subset analyses suggest that not all infiltrating T cells predict a positive outcome. In general, infiltration by CD8+ T cells predicts a positive outcome, while CD4+ cells predict a negative outcome. Therefore, the analysis of cellular phenotypes and potentially spatial distribution of infiltrating cells are critical for an accurate assessment of outcome. Similarly, cellular infiltration of metastatic foci is also a critical parameter for inducing therapeutic responses, as well as establishing tumor dormancy. Current strategies for cellular, gene, and molecular therapies are focused on the manipulation of infiltrating cellular populations. Within this review, we discuss the role of tumor infiltrating, myeloid-monocytic cells, and T lymphocytes, as well as their potential for tumor control, immunosuppression, and facilitation of metastasis.

Keywords

Macrophage Tumor infiltration Myeloid-derived suppressor cell Dendritic cell T lymphocyte Prognostic surrogate

Copyright information

© Springer Science+Business Media, LLC 2007