Commensal bacteria and fungi differentially regulate tumor responses to radiation therapy.
Commensal bacteria and fungi differentially regulate tumor responses to radiation therapy.
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共生细菌和真菌对肿瘤放疗反应有不同的调节作用。
DOI：
10.1016/j.ccell.2021.07.002
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发表时间：
2021-09-13
期刊：
影响因子：
50.3
通讯作者：
Underhill DM
中科院分区：
文献类型：
--
作者：
Shiao SL;Kershaw KM;Limon JJ;You S;Yoon J;Ko EY;Guarnerio J;Potdar AA;McGovern DPB;Bose S;Dar TB;Noe P;Lee J;Kubota Y;Maymi VI;Davis MJ;Henson RM;Choi RY;Yang W;Tang J;Gargus M;Prince AD;Zumsteg ZS;Underhill DM
研究表明，癌症化疗和免疫治疗的疗效受到肠道细菌的影响。然而，微生物组对放射治疗的影响并不清楚，微生物组包括的不仅仅是细菌。在这里，我们发现肠道真菌调节乳腺癌和黑色素瘤小鼠模型辐射后的抗肿瘤免疫反应，真菌和细菌对这些反应有相反的影响。抗生素介导的真菌耗竭或无菌排斥增强了对辐射的反应性，而抗生素介导的细菌耗竭降低了反应性，并与真菌的过度生长有关。此外，Dectin-1（真菌的主要先天传感器）的肿瘤内表达升高与乳腺癌患者的生存率呈负相关，并且是放射治疗小鼠模型中真菌作用所必需的。肿瘤细菌的消耗导致肿瘤真菌的扩张和肿瘤照射后抗肿瘤免疫力的降低。靶向真菌通过减少巨噬细胞介导的免疫抑制增强辐射诱导的抗肿瘤免疫应答。因此，Shiao等人证明了放射后肠道细菌和真菌对抗肿瘤免疫的相反作用。
Studies suggest that the efficacy of cancer chemotherapy and immunotherapy is influenced by intestinal bacteria. However, the influence of the microbiome on radiation therapy is not as well-understood, and the microbiome comprises more than bacteria. Here, we find that intestinal fungi regulate antitumor immune responses following radiation in mouse models of breast cancer and melanoma and that fungi and bacteria have opposite influences on these responses. Antibiotic mediated depletion or gnotobiotic exclusion of fungi enhances responsiveness to radiation, whereas antibiotic mediated depletion of bacteria reduces responsiveness and is associated with overgrowth of commensal fungi. Further, elevated intratumoral expression of Dectin-1, a primary innate sensor of fungi, is negatively associated with survival in patients with breast cancer and is required for the effects of commensal fungi in mouse models of radiation therapy. Depletion of commensal bacteria leads to expansion of commensal fungi and reduced anti-tumor immunity following irradiation of tumors. Targeting commensal fungi enhanced the radiation induced anti-tumor immune response by reducing macrophage mediated immunosuppression. Thus, Shiao et al demonstrates opposing effects of commensal bacteria and fungi on anti-tumor immunity following radiation.
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DOI：
10.1038/nri2569
发表时间：
2009-07
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Geijtenbeek TB;Gringhuis SI
通讯作者：
Gringhuis SI
DOI：
10.1007/978-1-4614-8244-4_10
发表时间：
2014-01-01
期刊：
METASTASIS RESEARCH PROTOCOLS, 2ND EDITION
影响因子：
--
作者：
Giavazzi, Raffaella;Decio, Alessandra
通讯作者：
Decio, Alessandra
影响因子：
82.9
作者：
Binnewies M;Roberts EW;Kersten K;Chan V;Fearon DF;Merad M;Coussens LM;Gabrilovich DI;Ostrand-Rosenberg S;Hedrick CC;Vonderheide RH;Pittet MJ;Jain RK;Zou W;Howcroft TK;Woodhouse EC;Weinberg RA;Krummel MF
通讯作者：
Krummel MF
影响因子：
32.4
作者：
Gur, Chamutal;Ibrahim, Yara;Isaacson, Batya;Yamin, Rachel;Abed, Jawad;Gamliel, Moriya;Enk, Jonatan;Bar-On, Yotam;Stanietsky-Kaynan, Noah;Coppenhagen-Glazer, Shunit;Shussman, Noam;Almogy, Gideon;Cuapio, Angelica;Hofer, Erhard;Mevorach, Dror;Tabib, Adi;Ortenberg, Rona;Markel, Gal;Miklic, Karmela;Jonjic, Stipan;Brennan, Caitlin A.;Garrett, Wendy S.;Bachrach, Gilad;Mandelboim, Ofer
通讯作者：
Mandelboim, Ofer
DOI：
10.1126/science.1221789
发表时间：
2012-06-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Iliev ID;Funari VA;Taylor KD;Nguyen Q;Reyes CN;Strom SP;Brown J;Becker CA;Fleshner PR;Dubinsky M;Rotter JI;Wang HL;McGovern DP;Brown GD;Underhill DM
通讯作者：
Underhill DM