| First Author | Naito T | Year | 2015 |
| Journal | Cancer Lett | Volume | 366 |
| Issue | 1 | Pages | 93-9 |
| PubMed ID | 26116901 | Mgi Jnum | J:223002 |
| Mgi Id | MGI:5646319 | Doi | 10.1016/j.canlet.2015.06.009 |
| Citation | Naito T, et al. (2015) High-dose cyclophosphamide induces specific tumor immunity with concomitant recruitment of LAMP1/CD107a-expressing CD4-positive T cells into tumor sites. Cancer Lett 366(1):93-9 |
| abstractText | 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. |
