The Hedgehog (HH) signaling pathway plays important roles in gastrointestinal carcinogenesis and the gastrointestinal tumor microenvironment (TME). Aberrant HH signaling activation may accelerate the growth of gastrointestinal tumors and lead to tumor immune tolerance and drug resistance. The interaction between HH signaling and the TME is intimately involved in these processes, for example, tumor growth, tumor immune tolerance, inflammation, and drug resistance. Evidence indicates that inflammatory factors in the TME, such as interleukin 6 (IL-6) and interferon-γ (IFN-γ), macrophages, and T cell-dependent immune responses, play a vital role in tumor growth by affecting the HH signaling pathway. Moreover, inhibition of proliferating cancer-associated fibroblasts (CAFs) and inflammatory factors can normalize the TME by suppressing HH signaling. Furthermore, aberrant HH signaling activation is favorable to both the proliferation of cancer stem cells (CSCs) and the drug resistance of gastrointestinal tumors. This review discusses the current understanding of the role and mechanism of aberrant HH signaling activation in gastrointestinal carcinogenesis, the gastrointestinal TME, tumor immune tolerance and drug resistance and highlights the underlying therapeutic opportunities.

刺猬（HH）信号通路在胃肠道癌变和胃肠道肿瘤微环境（TME）中起重要作用。异常的HH信号激活可能会加速胃肠道肿瘤的生长，并导致肿瘤的免疫耐受和耐药性。HH信号传导与TME之间的相互作用与这些过程密切相关，例如，肿瘤生长，肿瘤免疫耐受，炎症和耐药性。有证据表明，TME中的炎性因子，例如白介素6（IL-6）和干扰素-γ（IFN- γ）巨噬细胞和T细胞依赖性免疫反应通过影响HH信号通路在肿瘤生长中起着至关重要的作用。此外，抑制增殖的癌症相关成纤维细胞（CAF）和炎症因子可以通过抑制HH信号来使TME正常化。此外，异常的HH信号激活既有利于癌症干细胞（CSCs）的增殖，也有利于胃肠道肿瘤的耐药性。这篇综述讨论了目前对异常HH信号激活在胃肠道癌变，胃肠道TME，肿瘤免疫耐受和耐药性中的作用和机制的理解，并强调了潜在的治疗机会。