Inflammatory cell infiltration of tumors: Jekyll or Hyde

James E. Talmadge, Moses Donkor, Eric Scholar

Research output: Contribution to journalReview articlepeer-review

221 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)373-400
Number of pages28
JournalCancer and Metastasis Reviews
Volume26
Issue number3-4
DOIs
StatePublished - Dec 2007

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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