Massara Layal, Khairallah Camille, Yared Nathalie, Pitard Vincent, Rousseau Benoit, Izotte Julien, Giese Alban, Dubus Pierre, Gauthereau Xavier, Déchanet-Merville Julie, Capone Myriam
University of Bordeaux, CNRS, ImmunoConcEpT, UMR 5164, 33076 Bordeaux, France.
Equipe Labellisée Ligue Contre le Cancer, Toulouse, France.
Mol Ther Oncolytics. 2020 Jan 29;16:250-261. doi: 10.1016/j.omto.2020.01.007. eCollection 2020 Mar 27.
Human cytomegalovirus (HCMV) components are often found in tumors, but the precise relationship between HCMV and cancer remains a matter of debate. Pro-tumor functions of HCMV were described in several studies, but an association between HCMV seropositivity and reduced cancer risk was also evidenced, presumably relying on recognition and killing of cancer cells by HCMV-induced lymphocytes. This study aimed at deciphering whether CMV influences cancer development in an immune-independent manner. Using immunodeficient mice, we showed that systemic infection with murine CMV (MCMV) inhibited the growth of murine carcinomas. Surprisingly, MCMV, but not HCMV, also reduced human colon carcinoma development . , both viruses infected human cancer cells. Expression of human interferon-β () and nuclear domain () were induced in MCMV-infected, but not in HCMV-infected human colon cancer cells. These results suggest a decreased capacity of MCMV to counteract intrinsic defenses in the human cellular host. Finally, immunodeficient mice receiving peri-tumoral MCMV therapy showed a reduction of human colon cancer cell growth, albeit no clinical sign of systemic virus dissemination was evidenced. Our study, which describes a selective advantage of MCMV over HCMV to control human colon cancer, could pave the way for the development of CMV-based therapies against cancer.
人巨细胞病毒(HCMV)成分常在肿瘤中被发现,但HCMV与癌症之间的确切关系仍存在争议。多项研究描述了HCMV的促肿瘤功能,但也有证据表明HCMV血清阳性与降低癌症风险之间存在关联,这可能依赖于HCMV诱导的淋巴细胞对癌细胞的识别和杀伤。本研究旨在破解CMV是否以免疫非依赖方式影响癌症发展。利用免疫缺陷小鼠,我们发现鼠巨细胞病毒(MCMV)全身感染可抑制鼠癌生长。令人惊讶的是,MCMV而非HCMV也能减少人结肠癌的发展。两种病毒均可感染人癌细胞。在MCMV感染的人结肠癌细胞中可诱导人β干扰素()和核结构域()表达,而在HCMV感染的细胞中则不能。这些结果表明MCMV对抗人细胞宿主固有防御的能力降低。最后,接受瘤周MCMV治疗的免疫缺陷小鼠显示人结肠癌细胞生长减少,尽管未发现全身病毒播散的临床迹象。我们的研究描述了MCMV相对于HCMV在控制人结肠癌方面的选择性优势,可为开发基于CMV的癌症治疗方法铺平道路。