Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10899516 | Cancer Letters | 2015 | 7 Pages |
Abstract
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.
Keywords
FCMDLNcytolytic T cellHprtCFSETregsCTXAPCGAPDHMFIFITCCC chemokineCD4+ T cellCTLsHCCallophycocyaninRegulatory T cellsCyclophosphamidefluorescein isothiocyanateFlow cytometrycytolytic T lymphocytesmean fluorescence intensityhypoxanthine phosphoribosyltransferaseHepatocellular carcinomaDraining lymph nodeglyceraldehyde-3-phosphate dehydrogenase
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Cancer Research
Authors
Tatsushi Naito, Tomohisa Baba, Kazuyoshi Takeda, Soichiro Sasaki, Yasunari Nakamoto, Naofumi Mukaida,