Targeting the tumour immune microenvironment (TIME) by cancer immunotherapy has led to improved patient outcomes. However, response to these treatments is heterogeneous and cancer-type dependant. The therapeutic activity of classical cancer therapies such as chemotherapy, radiotherapy, and surgical oncology is modulated by alterations of the TIME. A major regulator of immune cell function and resistance to both immune and classical therapies is the extracellular matrix (ECM). Concurrently, cancer therapies reshape the TIME as well as the ECM, causing both pro- and anti-tumour responses. Accordingly, the TIME-ECM crosstalk presents attractive opportunities to improve therapy outcomes. Here, we review the molecular crosstalk between the TIME and the ECM in cancer and its implications in cancer progression and clinical intervention. Additionally, we discuss examples and future directions of ECM and TIME co-targeting in combination with oncological therapies including surgery, chemotherapy, and radiotherapy.

通过癌症免疫疗法瞄准肿瘤免疫微环境（TIME）已改善了患者的治疗效果。然而，对这些治疗的反应是异质的并且取决于癌症类型。经典癌症疗法（例如化疗、放疗和肿瘤外科手术）的治疗活性是通过 TIME 的改变来调节的。细胞外基质（ECM）是免疫细胞功能以及对免疫和经典疗法的抵抗力的主要调节剂。同时，癌症疗法重塑了 TIME 和 ECM，从而引起促肿瘤反应和抗肿瘤反应。因此，TIME-ECM 串扰为改善治疗结果提供了诱人的机会。在这里，我们回顾了癌症中 TIME 和 ECM 之间的分子串扰及其对癌症进展和临床干预的影响。此外，我们还讨论了 ECM 和 TIME 联合靶向与肿瘤治疗（包括手术、化疗和放疗）相结合的示例和未来方向。