Role and therapeutic potential of CC and CXC chemokines in the tumor microenvironment

doi:10.3760/cma.j.cn371439-20250528-00037

Abstract

Abstract:

Chemokines are a class of cytokines with chemotactic functions that play important roles in the tumor microenvironment through receptor binding. Their functional mechanisms in tumor progression mainly include activating signaling pathways to promote tumor cell proliferation and metastasis， regulating tumor angiogenesis to alter blood supply and nutritional status， and mediating immune escape to evade host defense systems. Studies have demonstrated that targeting specific chemokine-receptor axes can effectively inhibit malignant behaviors of tumor cells and regulate immune cell infiltration， showing significant anti-tumor effects. Research on the critical roles of CC and CXC chemokines regulatory networks in the tumor microenvironment and their targeted therapeutic strategies provides an important theoretical basis and clinical application prospects for the treatment of malignant tumors.

Key words: Chemokines， CC, Chemokines， CXC, Tumor microenvironment, Tumor escape, Immunotherapy

Yang Xinru, Cao Lili. Role and therapeutic potential of CC and CXC chemokines in the tumor microenvironment[J]. Journal of International Oncology, 2026, 53(4): 224-228.

Figures/Tables 1

References 55

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典型成员	主要受体	高表达肿瘤类型	TME中的核心功能	临床关联性与治疗策略
CC亚家族
CCL2	CCR2	胰腺癌^[6]、乳腺癌、胶质瘤^[7]	招募肿瘤相关巨噬细胞（M2型）、促进血管生成、免疫抑制	放疗+抗PD-1抗体+CCR2/5抑制剂联合疗法可显著提高胰腺癌的抗肿瘤疗效^[6]
CCL3	CCR1/CCR5	食管鳞状细胞癌^[8]、结直肠癌^[9]	促进肿瘤相关巨噬细胞浸润、增强肿瘤侵袭性	CCR1拮抗剂（CCX721）可抑制骨髓瘤转移^[10]
CCL5	CCR5	乳腺癌^[11]、胃癌^[12]、前列腺癌^[13]	诱导调节性T细胞/髓源性抑制细胞募集、促进远处转移	CCR5抑制剂（马拉维罗）可显著改善结直肠癌肝转移模型的治疗效果^[14]
CCL18	CCR8	卵巢癌^[15]	驱动上皮间质转化、增强肿瘤相关巨噬细胞介导的免疫逃逸	抗CCR8单克隆抗体与PD-1抑制剂联合使用可显著抑制非小细胞肺癌肿瘤的生长^[16]
CXC亚家族
CXCL1	CXCR2	黑色素瘤、乳腺癌、肺癌、胰腺癌、结直肠癌、肝癌^[17]	招募中性粒细胞、促进血管生成	CXCR2抑制剂（AZD5069）可提升抗PD-1免疫疗法对胃癌的抗肿瘤疗效^[18]
CXCL8	CXCR1/2	胃癌、卵巢癌、结直肠癌、乳腺癌、前列腺癌^[19]	上调PD-L1、抑制CD8⁺ T细胞功能	CXCR2抑制剂通过抑制CXCL8/CXCR2信号通路可有效减缓乳腺癌的生长^[20]
CXCL12	CXCR4/7	结直肠癌^[21]、前列腺癌^[22]	介导肿瘤干细胞休眠、保护化疗抵抗	CXCL12抑制剂（NOX-A12）与帕博利珠单抗联合对微卫星稳定转移性结直肠癌和胰腺癌有显著的疗效^[23]