Immune infiltration in human tumors: a prognostic factor that should not be ignored
Top Cited Papers
- 30 November 2009
- journal article
- review article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 29 (8), 1093-1102
- https://doi.org/10.1038/onc.2009.416
Abstract
The natural history of a tumor includes phases of ‘in situ’ growth, invasion, extravasation and metastasis. During these phases, tumor cells interact with their microenvironment and are influenced by signals coming from stromal, endothelial, inflammatory and immune cells. Indeed, tumors are often infiltrated by various numbers of lymphocytes, macrophages or mast cells. It is generally believed that the latter produce factors that maintain chronic inflammation and promote tumor growth, whereas lymphocytes may control cancer outcome, as evidenced in mouse models. In this study, we analyze data from large cohorts of human tumors, clearly establishing that infiltration of the primary tumor by memory T cells, particularly of the Th1 and cytotoxic types, is the strongest prognostic factor in terms of freedom from disease and overall survival at all stages of clinical disease. We review data suggesting that tertiary lymphoid structures adjacent to tumors and composed of mature dendritic cells (T and B cells organized as germinal centers) may be the site of an antitumor reaction. We propose an immune scoring based on the type, density and location of lymphocyte infiltrates as a novel prognostic factor for use in addition to tumor node metastasis staging to predict disease-free survival and to aid in decisions regarding adjuvant therapies in early stage human cancers.Keywords
This publication has 91 references indexed in Scilit:
- Heterogeneity of natural Foxp3 + T cells: A committed regulatory T-cell lineage and an uncommitted minor population retaining plasticityProceedings of the National Academy of Sciences of the United States of America, 2009
- High density of FOXP3-positive T cells infiltrating colorectal cancers with microsatellite instabilityBritish Journal of Cancer, 2008
- Ectopic lymphoid tissues and local immunitySeminars in Immunology, 2008
- CD8 tumor-infiltrating lymphocytes are predictive of survival in muscle-invasive urothelial carcinomaProceedings of the National Academy of Sciences of the United States of America, 2007
- Metronomic cyclophosphamide regimen selectively depletes CD4+CD25+ regulatory T cells and restores T and NK effector functions in end stage cancer patientsCancer Immunology, Immunotherapy, 2006
- Concurrent infiltration by CD8+ T cells and CD4+ T cells is a favourable prognostic factor in non-small-cell lung carcinomaBritish Journal of Cancer, 2006
- The Three Es of Cancer ImmunoeditingAnnual Review of Immunology, 2004
- Inflammation and cancerNature, 2002
- Cancer immunoediting: from immunosurveillance to tumor escapeNature Immunology, 2002
- The Hallmarks of CancerCell, 2000