Adjuvant-mediated tumor regression and tumor-specific cytotoxic response are impaired in MyD88-deficient mice - PubMed (original) (raw)

. 2004 Jan 15;64(2):757-64.

doi: 10.1158/0008-5472.can-03-1518.

Hisayo Masuda, Yoshiko Saeki, Misako Matsumoto, Kiyoshi Takeda, Kunio Tsujimura, Kiyotaka Kuzushima, Toshitada Takahashi, Ichiro Azuma, Shizuo Akira, Kumao Toyoshima, Tsukasa Seya

Affiliations

Adjuvant-mediated tumor regression and tumor-specific cytotoxic response are impaired in MyD88-deficient mice

Takashi Akazawa et al. Cancer Res. 2004.

Abstract

The Mycobacterium bovis bacillus Calmette-Guérin cell-wall skeleton (BCG-CWS) activates Toll-like receptor (TLR) 2 and TLR4, but unlike the typical TLR4 agonist bacterial lipopolysaccharide barely induces type 1 IFN. BCG-CWS has been used for adjuvant immunotherapy for patients with cancer. We investigated the adjuvant potential of BCG-CWS for induction of CTLs subsequent to TLR-mediated dendritic cell (DC) maturation, using a syngeneic mouse tumor model (B16 melanoma in C57BL/6). We evaluated the retardation of tumor growth and cytotoxic response in wild-type and MyD88-/- mice immunized with tumor debris and/or BCG-CWS. Delays in tumor growth and cytotoxic response were induced by immunization with a mixture of BCG-CWS emulsion and the tumor. BCG-CWS was capable of activating DCs ex vivo by the criteria of CD80/CD86 up-regulation and cytokine (interleukin-12, tumor necrosis factor-alpha) induction. Efficient tumor suppression and ex vivo cytokine induction did not occur in MyD88-deficient mice and cells, suggesting that the MyD88 adapter is crucial for induction of tumor cytotoxicity. Because TLR4 is involved in both MyD88-dependent and -independent pathways and the latter affects DC maturation, our findings indicate that both pathways cooperate to induce CTL-based tumor immunity.

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