The host immune system shapes the fate of tumor progression. Hence, manipulating patients' immune system to activate host immune responses against cancer pathogenesis is a promising strategy to develop effective therapeutic interventions for metastatic and drug resistant cancers. Understanding the dynamic mechanisms within the tumor microenvironment (TME) that contribute to heterogeneity and metabolic plasticity is essential to enhance the patients' responsiveness to immune targeted therapies. Riera-Domingo et. al. describe the immune landscape within the TME, and highlight the significance of metabolic and hypoxic signatures that impact immune function and response to immunotherapy. Current literature in this field confirms that targeting tumor metabolism and the acidic microenvironment commonly associated with tumors may present as viable strategies to modulate the host immune system in favor of developing highly effective immune targeted therapies. However, development of better tools to understand tumor-immune interactions and identify mechanisms driving non-responders, more innovative clinical trial design, and new therapies will need to be identified to move the field forward. Personalized immune therapies incorporating metabolic and microbiome-based gene signatures to influence the therapeutic response and novel methods to generate immunologically "hot" tumors are at the forefront of immunotherapy currently. The combination of these approaches with clinically approved immunotherapies will also be valuable moving forward.

中文翻译：

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以 TME 为目标推进免疫治疗。

宿主免疫系统决定了肿瘤进展的命运。因此，操纵患者的免疫系统以激活针对癌症发病机制的宿主免疫反应是开发有效的转移性和耐药性癌症治疗干预措施的有前景的策略。了解肿瘤微环境 (TME) 中导致异质性和代谢可塑性的动态机制对于增强患者对免疫靶向治疗的反应至关重要。里埃拉-多明戈等。人。描述 TME 内的免疫情况，并强调影响免疫功能和对免疫治疗反应的代谢和缺氧特征的重要性。该领域的当前文献证实，靶向肿瘤代谢和通常与肿瘤相关的酸性微环境可能是调节宿主免疫系统的可行策略，有利于开发高效的免疫靶向治疗。然而，需要开发更好的工具来了解肿瘤-免疫相互作用并确定驱动无反应者的机制、更具创新性的临床试验设计和新疗法，以推动该领域的发展。结合代谢和基于微生物组的基因特征来影响治疗反应的个性化免疫疗法和产生免疫“热”肿瘤的新方法是目前免疫疗法的前沿。