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The biologic importance of tumor-infiltrating lymphocytes

Authors

  • F. Stephen Hodi,

    1. Department of Medical Oncology and Cancer Vaccine Center, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
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  • Glenn Dranoff

    Corresponding author
    1. Department of Medical Oncology and Cancer Vaccine Center, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
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Glenn Dranoff, Dana-Farber Cancer Institute, Dana 520C, 44 Binney Street, Boston, MA 02115, USA
Tel: +617 632 5051
Fax: +617 632 5167
e-mail: glenn_dranoff@dfci.harvard.edu

Abstract

Detailed pathologic analysis has delineated a close association between intratumoral CD 8+ cytotoxic T cells and favorable clinical outcomes in diverse cancers. Conversely, the presence at tumor sites of negative immune regulatory elements, such as FoxP 3+ T cells (Tregs) and PD-1/PD-L1 co-stimulatory molecules, is closely associated with inferior patient survival. Together, these results indicate the importance of the balance between cytotoxic and regulatory pathways in the tumor microenvironment as a critical determinant of prognosis. This immune index also provides a framework for devising therapeutic strategies to enlarge the population of antitumor cytotoxic T cells and attenuate immune regulation. Among these approaches, vaccination with irradiated, autologous tumor cells engineered to secrete granulocyte–macrophage colony-stimulating factor (GM-CSF) followed by antibody blockade of cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) provides clinical benefits for some advanced-course melanoma patients. The extent of tumor necrosis in post-treatment biopsies is linearly related to the natural logarithm of the ratio of CD 8+ T cells to FoxP 3+ Tregs. These findings show a concordance between the immune signature of tumor protection in endogenous and therapy-induced responses, strongly supporting Martin Mihm's original insights.

Hodi FS, Dranoff G. The biologic importance of tumor-infiltrating lymphocytes.

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