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Progression of carcinogen‐induced fibrosarcomas is associated with the accumulation of naïve CD4+ T cells via blood vessels and lymphatics

This paper was not found in any repository, but could be made available legally by the author.
This paper was not found in any repository, but could be made available legally by the author.

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Abstract

The tumor microenvironment comprises newly formed blood and lymphatic vessels which shape the influx, retention and departure of lymphocytes within the tumor mass. Thus, by influencing the intra-tumoral composition of lymphocytes, these vessels affect the manner in which the adaptive immune system responds to the tumor, either promoting or impairing effective anti-tumor immunity. In this study we utilised a mouse model of carcinogen-induced fibrosarcoma to examine the composition of tumor-infiltrating lymphocytes (TILs) during tumor progression. In particular, we sought to determine whether CD4(+) Foxp3(+) regulatory T cells (Tregs) became enriched during tumor progression thereby contributing to tumor-driven immunosuppression. This was not the case as the proportion of Tregs and effector CD4(+) T cells actually declined within the tumor due to the unexpected accumulation of naïve T cells. However, we found no evidence for antigen-driven migration of these T cells or for their participation in an anti-tumor immune response. Our data support the notion that lymphocytes can enter tumors via aberrantly formed blood and lymphatic vessels. Such findings suggest that targeting both the tumor vasculature and lymphatics will alter the balance of lymphocyte sub-populations that enter the tumor mass. A consideration of this aspect of tumor immunology may be critical to the success of solid cancer immunotherapies. © 2013 Wiley Periodicals, Inc.