多重证据表明，从动物模型到人类临床试验，微生物组影响癌症免疫疗法的反应。虽然最初的研究专注于肠道微生物群肿瘤轴，但最近的研究还考察了位于肿瘤细胞内或肿瘤微环境中的细菌对癌症治疗反应的介导作用。令人惊讶的是，这一现象在传统上被认为没有定居微生物群的解剖部位中的癌症中已得到证实。在《癌症研究》杂志的这一期中，吴等人研究了食管鳞状细胞癌（ESCC）新辅助化疗联合免疫疗法（NACI）治疗中肿瘤内细菌特征对治疗反应的影响。该研究报告称，肿瘤内链球菌，可能是由于肠道细菌转位导致，预测了小鼠模型以及ESCC患者中NACI的治疗效果。这些新发现进一步强调了肿瘤免疫微环境和免疫疗法疗效都受肿瘤内微生物及其相关代谢产物的影响的可能性。这些发现还引起了肿瘤和细菌抗原之间可能的交叉反应的有趣可能性。鉴于肠道微生物组通过饮食、益生元/益生菌和粪菌移植等策略可能是可调节的因素，进一步探究肠道和/或肿瘤内细菌影响抗肿瘤免疫的机制是非常有必要的。详见吴等人的相关文章，第3131页。©2023年美国癌症研究协会。

Multiple lines of evidence spanning from animal models to human clinical trials indicate that the microbiome influences cancer immunotherapy response. Whereas initial studies focused exclusively on the gastrointestinal (gut) microbiota-tumor axis, more recent studies have examined the possibility that bacteria located within tumor cells or within the tumor microenvironment mediate cancer treatment response. Strikingly, this phenomenon has been demonstrated in cancers that arise in anatomic locations that are traditionally thought to be devoid of resident microbiota. In this issue of Cancer Research, Wu and colleagues examine the effects of intratumoral bacterial signatures on treatment response in the setting of neoadjuvant chemotherapy combined with immunotherapy (NACI) in the treatment of esophageal squamous cell carcinoma (ESCC). The study reports that intratumoral Streptococcus, presumably due to bacterial translocation from the gut, predicts the treatment efficacy of NACI in murine models as well as individuals with ESCC. These new findings further highlight the possibility that the presence of intratumoral microbes as well as their associated metabolites influence both the tumor immune microenvironment and immunotherapy efficacy. These findings also raise the intriguing possibility of cross-reactivity between tumor and bacterial antigens. Given that the gut microbiome is potentially a modifiable factor via diet, prebiotics/probiotics, and fecal microbiota transplantation, among other strategies, further exploration into the mechanisms by which gut and/or intratumoral bacteria influence antitumor immunity is certainly warranted. See related article by Wu et al., p. 3131.©2023 American Association for Cancer Research.