Tumor-Infiltrating Lymphocytes and Their Role in Solid Tumor Progression
Tumor-infiltrating lymphocytes (TIL) are an important component of the tumor environment. Their role in tumor growth and progression has been debated for decades, with the current emphasis on survival benefits TIL appear to bestow on the host when present
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Tumor-Infiltrating Lymphocytes and Their Role in Solid Tumor Progression Theresa L. Whiteside
Abstract Tumor-infiltrating lymphocytes (TIL) are an important component of the tumor environment. Their role in tumor growth and progression has been debated for decades, with the current emphasis on survival benefits TIL appear to bestow on the host when present in situ as large aggregates of activated T and B cells. Gene signatures and protein profiling of TIL provide clues about their potential functions in the tumor, and correlations with clinicopathological tumor characteristics, clinical outcome, and patients’ survival data indicate that TIL exert influence on the disease progression, especially in colorectal carcinomas and breast cancer. At the same time, the recognition that TIL signatures vary in composition and with time, and that TIL interactions with the tumor cells are complex, calls for a more careful assessment of their prognostic significance. The mechanisms tumors utilize to subvert the host immune system are well-known. The balance between pro- and anti-tumor responses of TIL might be orchestrated by the tumor serving as a measure of its aggressiveness and potentially providing a key to selecting therapeutic strategies and to prognosis. Keywords Cancer • Tumor-infiltrating cells • Lymphocytes • Prognosis
List of Abbreviations Ab ADCC CFC
Antibody Antibody-dependent cellular cytotoxicity Cytokine flow cytometry
T.L. Whiteside (*) Department of Pathology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, 5117 Centre Avenue, Suite 1.27, Pittsburgh, PA 15213, USA Department of Immunology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, 5117 Centre Avenue, Suite 1.27, Pittsburgh, PA 15213, USA e-mail: [email protected] M. Klink (ed.), Interaction of Immune and Cancer Cells, DOI 10.1007/978-3-7091-1300-4_6, © Springer-Verlag Wien 2014
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CRC CTL CTLA-4 DC ER IGKC MDSC MHC NK NSCLC PD-1 PGE2 PMN TA TCR TGF-β Th cell TIL TMA Treg VEGF
Colorectal cancer Cytolytic T cell Cytotoxic T lymphocyte-associated antigen-4 Dendritic cells Estrogen receptor IgG kappa chain Myeloid-derived suppressor cells Major histocompatibility complex Natural killer cells Non-small cell lung cancer Programmed cell death protein-1 Prostaglandin E2 Polymorphonuclear neutrophils Tumor-associated antigen T-cell receptor Transforming growth factor-β T helper cell Tumor-infiltrating lymphocytes Tissue microarrays Regulatory T cells Vascular endothelial growth factor
Contents 6.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.2 Anti-tumor Effects of TIL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.2.1 CD8+ Cytolytic T Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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