肿瘤相关巨噬细胞(TAMs)是影响肿瘤化疗药敏感性的关键因素。我们在食管鳞癌（ESCC）临床标本及细胞水平研究初步表明TAMs源性CCL22是减低顺铂敏感性的重要细胞因子，其机制可能与其激活癌细胞中CCR4/FAK/Akt通路有关。我们发表在Oncogene上的文章证实DGKα与FAK上FERM结构域结合，使得Tyr397位点暴露而自磷酸化激活，进而激活下游Akt。CCL22可诱导CCR4分别与DGKα及FAK结合。目前已知：抑制Akt可增强肿瘤化疗药敏感性。综上，我们提出假设：CCL22作用于ESCC细胞中CCR4，以CCR4为支架蛋白募集DGKα及FAK，易化DGKα与FAK结合，增强DGKα释放FAK自磷酸化抑制的效应，激活FAK/Akt通路，减低ESCC顺铂敏感性。本研究将揭示TAMs中一个新的调控癌细胞顺铂敏感性的细胞因子，并为临床从微环境角度研究增敏化疗药抗癌策略提供实验依据。

Tumor-associated macrophages (TAMs) are the key factors affecting chemosensitivity of tumors. Our preliminary studies on clinical specimens and cell level of esophageal squamous cell carcinoma (ESCC) indicate that TAMs-derived CCL22 is an important cytokine to reduce cisplatin sensitivity, and the molecular mechanism may be related to its activation of CCR4/FAK/Akt pathway in cancer cells. Our article published in 《Oncogene》 confirms that DGKα binds to the FERM domain on FAK, exposing Tyr397 site to self-phosphorylation and subsequently activating downstream Akt. CCL22 can induce CCR4 to directly bind to DGKα and FAK, respectively. It is known that inhibition of Akt activity can enhance the sensitivity of cancer chemotherapeutics. In conclusion, we hypothesize that CCL22 acts on CCR4 in ESCC cells, recruits DGKα and FAK with CCR4 as scaffold protein, facilitates the binding of DGKα to FAK, releases the inhibition of FAK autophosphorylation by DGKα, activates FAK/Akt pathway, and reduces the sensitivity of ESCC to cisplatin. This study will reveal a new cytokine in TAMs that regulates the sensitivity of cancer cells to cisplatin, and provide experimental basis for the clinical study of anti-cancer strategies of sensitized chemotherapeutic agents from the perspective of microenvironment.