学術雑誌論文 High-dose cyclophosphamide induces specific tumor immunity with concomitant recruitment of LAMP1/CD107a-expressing CD4-positive T cells into tumor sites

Naito, Tatsushi  ,  Baba, Tomohisa  ,  Takeda, Kazuyoshi  ,  Sasaki, Soichiro  ,  Nakamoto, Yasunari  ,  Mukaida, Naofumi

366 ( 1 )  , pp.93 - 99 , 2015-09-28 , Elsevier Ireland Ltd.
ISSN:0304-3835
NII書誌ID(NCID):AA00598513
内容記述
Cancer chemotherapy regimens, particularly those employing high-dose cytotoxic drugs such as cyclophosphamide (CTX), have been considered to be immune suppressive. However, we observed that a single administration of high-dose CTX abolished tumors arising from subcutaneous injection of a mouse hepatoma cell line and subsequently induced specific tumor immunity. Depletion of T cells, specifically CD4+ T cells, abrogated the CTX-mediated tumor regression. CTX treatment induced the rapid recruitment of CD4+ T cells into the tumors, and these recruited cells initiated expression of LAMP1/CD107a, a cytotoxic granule molecule, and granzyme B in the absence of antigen presentation at draining lymph nodes and proliferation in the tumor tissues. Moreover, CTX enhanced the expression of a CC chemokine, CCL3, in tumor tissues, and CTX-mediated tumor regression was attenuated in mice deficient in CCR5, the receptor for this chemokine. Consistently, less CTX-induced accumulation of intratumoral LAMP1/CD107a-expressing CD4+ T cells was observed in mice receiving splenocytes derived from CCR5-deficient mice than in those receiving splenocytes derived from WT mice. Thus, CTX induces the expression of CCL3, which induces the intratumoral migration of CD4+ T cells expressing cytotoxic molecules, leading to tumor eradication and subsequent specific tumor immunity. © 2015 Elsevier Ireland Ltd.
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http://dspace.lib.kanazawa-u.ac.jp/dspace/bitstream/2297/43441/1/CA-PR-MUKAIDA-N-93.pdf

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