@article{oai:kanazawa-u.repo.nii.ac.jp:00027476,
 author = {Naito, Tatsushi and Baba, Tomohisa and Takeda, Kazuyoshi and Sasaki, Soichiro and Nakamoto, Yasunari and Mukaida, Naofumi},
 issue = {1},
 journal = {Cancer Letters},
 month = {Sep},
 note = {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., 12 months Embargo},
 pages = {93--96},
 title = {High-dose cyclophosphamide induces specific tumor immunity with concomitant recruitment of LAMP1/CD107a-expressing CD4-positive T cells into tumor sites},
 volume = {336},
 year = {2015}
}