Targeting cytokine/chemokine signaling to convert immunologically cold tumors into hot: Emerging strategies in cancer immunotherapy.....
3.14. CCL5/CCR5 axis
CCL5 is a chemokine that is primarily secreted by inflammatory cells, including T cells and monocytes174. This axis facilitates the recruitment of Tregs, MDSCs, and TAMs, creating an immunosuppressive TME that promotes tumor progression and evasion of immune surveillance175, 176, 177. In metastatic CRC, increased CCL5/CCR5 signaling correlates with higher infiltration of Tregs and MDSCs, which can lead to resistance to immune checkpoint blockade therapies178. In addition, a combination therapy of a CCL5 inhibitor and ICIs has been shown to reprogram the immunosuppressive TME and enhance anti-tumor efficacy in CRC179. Similarly, inhibiting the CCL5/CCR5 axis in TNBC reduces immature myeloid cells, underscoring its potential as a therapeutic target180. Preclinical studies have demonstrated that CCR5 antagonists, such as Maraviroc, potentiate the effects of ICIs and chemotherapeutic agents by reprogramming the TME to support anti-tumor immunity181. CCR5 antagonists, including Maraviroc and Leronlimab, as well as dual CCR2/CCR5 inhibitors such as cenicriviroc, are undergoing early-phase clinical evaluation, often in combination with ICIs or chemotherapy, supporting their translational potential182. Thus, targeting the CCL5/CCR5 axis could improve cancer treatment outcomes by impeding the infiltration of immunosuppressive cells and enhancing immune effector responses.
https://www.sciencedirect.com/science/article...352600170X
3.14. CCL5/CCR5 axis
CCL5 is a chemokine that is primarily secreted by inflammatory cells, including T cells and monocytes174. This axis facilitates the recruitment of Tregs, MDSCs, and TAMs, creating an immunosuppressive TME that promotes tumor progression and evasion of immune surveillance175, 176, 177. In metastatic CRC, increased CCL5/CCR5 signaling correlates with higher infiltration of Tregs and MDSCs, which can lead to resistance to immune checkpoint blockade therapies178. In addition, a combination therapy of a CCL5 inhibitor and ICIs has been shown to reprogram the immunosuppressive TME and enhance anti-tumor efficacy in CRC179. Similarly, inhibiting the CCL5/CCR5 axis in TNBC reduces immature myeloid cells, underscoring its potential as a therapeutic target180. Preclinical studies have demonstrated that CCR5 antagonists, such as Maraviroc, potentiate the effects of ICIs and chemotherapeutic agents by reprogramming the TME to support anti-tumor immunity181. CCR5 antagonists, including Maraviroc and Leronlimab, as well as dual CCR2/CCR5 inhibitors such as cenicriviroc, are undergoing early-phase clinical evaluation, often in combination with ICIs or chemotherapy, supporting their translational potential182. Thus, targeting the CCL5/CCR5 axis could improve cancer treatment outcomes by impeding the infiltration of immunosuppressive cells and enhancing immune effector responses.
https://www.sciencedirect.com/science/article...352600170X
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