Roles of the CXCL8-CXCR1/2 Axis in the Tumor Microenvironment and Immunotherapy
In humans, Interleukin-8 (IL-8 or CXCL8) is a granulocytic chemokine with multiple roles within the tumor microenvironment (TME), such as recruiting immunosuppressive cells to the tumor, increasing tumor angiogenesis, and promoting epithelial-to-mesenchymal transition (EMT). All of these effects of...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-12-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/27/1/137 |
| _version_ | 1797498293460140032 |
|---|---|
| author | Zhi-Jian Han Yang-Bing Li Lu-Xi Yang Hui-Juan Cheng Xin Liu Hao Chen |
| author_facet | Zhi-Jian Han Yang-Bing Li Lu-Xi Yang Hui-Juan Cheng Xin Liu Hao Chen |
| author_sort | Zhi-Jian Han |
| collection | DOAJ |
| description | In humans, Interleukin-8 (IL-8 or CXCL8) is a granulocytic chemokine with multiple roles within the tumor microenvironment (TME), such as recruiting immunosuppressive cells to the tumor, increasing tumor angiogenesis, and promoting epithelial-to-mesenchymal transition (EMT). All of these effects of CXCL8 on individual cell types can result in cascading alterations to the TME. The changes in the TME components such as the cancer-associated fibroblasts (CAFs), the immune cells, the extracellular matrix, the blood vessels, or the lymphatic vessels further influence tumor progression and therapeutic resistance. Emerging roles of the microbiome in tumorigenesis or tumor progression revealed the intricate interactions between inflammatory response, dysbiosis, metabolites, CXCL8, immune cells, and the TME. Studies have shown that CXCL8 directly contributes to TME remodeling, cancer plasticity, and the development of resistance to both chemotherapy and immunotherapy. Further, clinical data demonstrate that CXCL8 could be an easily measurable prognostic biomarker in patients receiving immune checkpoint inhibitors. The blockade of the CXCL8-CXCR1/2 axis alone or in combination with other immunotherapy will be a promising strategy to improve antitumor efficacy. Herein, we review recent advances focusing on identifying the mechanisms between TME components and the CXCL8-CXCR1/2 axis for novel immunotherapy strategies. |
| first_indexed | 2024-03-10T03:31:24Z |
| format | Article |
| id | doaj.art-f90c9bccfd3a47f4a5529b61e3d2f963 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T03:31:24Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-f90c9bccfd3a47f4a5529b61e3d2f9632023-11-23T11:57:15ZengMDPI AGMolecules1420-30492021-12-0127113710.3390/molecules27010137Roles of the CXCL8-CXCR1/2 Axis in the Tumor Microenvironment and ImmunotherapyZhi-Jian Han0Yang-Bing Li1Lu-Xi Yang2Hui-Juan Cheng3Xin Liu4Hao Chen5The Key Laboratory of the Digestive System Tumors of Gansu Province, Tumor Center, Lanzhou University Second Hospital, Lanzhou 730000, ChinaThe Key Laboratory of the Digestive System Tumors of Gansu Province, Tumor Center, Lanzhou University Second Hospital, Lanzhou 730000, ChinaThe Key Laboratory of the Digestive System Tumors of Gansu Province, Tumor Center, Lanzhou University Second Hospital, Lanzhou 730000, ChinaThe Key Laboratory of the Digestive System Tumors of Gansu Province, Tumor Center, Lanzhou University Second Hospital, Lanzhou 730000, ChinaThe Second Clinical Medical College, Lanzhou University, Lanzhou 730000, ChinaThe Key Laboratory of the Digestive System Tumors of Gansu Province, Tumor Center, Lanzhou University Second Hospital, Lanzhou 730000, ChinaIn humans, Interleukin-8 (IL-8 or CXCL8) is a granulocytic chemokine with multiple roles within the tumor microenvironment (TME), such as recruiting immunosuppressive cells to the tumor, increasing tumor angiogenesis, and promoting epithelial-to-mesenchymal transition (EMT). All of these effects of CXCL8 on individual cell types can result in cascading alterations to the TME. The changes in the TME components such as the cancer-associated fibroblasts (CAFs), the immune cells, the extracellular matrix, the blood vessels, or the lymphatic vessels further influence tumor progression and therapeutic resistance. Emerging roles of the microbiome in tumorigenesis or tumor progression revealed the intricate interactions between inflammatory response, dysbiosis, metabolites, CXCL8, immune cells, and the TME. Studies have shown that CXCL8 directly contributes to TME remodeling, cancer plasticity, and the development of resistance to both chemotherapy and immunotherapy. Further, clinical data demonstrate that CXCL8 could be an easily measurable prognostic biomarker in patients receiving immune checkpoint inhibitors. The blockade of the CXCL8-CXCR1/2 axis alone or in combination with other immunotherapy will be a promising strategy to improve antitumor efficacy. Herein, we review recent advances focusing on identifying the mechanisms between TME components and the CXCL8-CXCR1/2 axis for novel immunotherapy strategies.https://www.mdpi.com/1420-3049/27/1/137interleukin-8chemokinetumor microenvironmentcancer-associated fibroblastmicrobiomeCXC receptors 1 and 2 |
| spellingShingle | Zhi-Jian Han Yang-Bing Li Lu-Xi Yang Hui-Juan Cheng Xin Liu Hao Chen Roles of the CXCL8-CXCR1/2 Axis in the Tumor Microenvironment and Immunotherapy Molecules interleukin-8 chemokine tumor microenvironment cancer-associated fibroblast microbiome CXC receptors 1 and 2 |
| title | Roles of the CXCL8-CXCR1/2 Axis in the Tumor Microenvironment and Immunotherapy |
| title_full | Roles of the CXCL8-CXCR1/2 Axis in the Tumor Microenvironment and Immunotherapy |
| title_fullStr | Roles of the CXCL8-CXCR1/2 Axis in the Tumor Microenvironment and Immunotherapy |
| title_full_unstemmed | Roles of the CXCL8-CXCR1/2 Axis in the Tumor Microenvironment and Immunotherapy |
| title_short | Roles of the CXCL8-CXCR1/2 Axis in the Tumor Microenvironment and Immunotherapy |
| title_sort | roles of the cxcl8 cxcr1 2 axis in the tumor microenvironment and immunotherapy |
| topic | interleukin-8 chemokine tumor microenvironment cancer-associated fibroblast microbiome CXC receptors 1 and 2 |
| url | https://www.mdpi.com/1420-3049/27/1/137 |
| work_keys_str_mv | AT zhijianhan rolesofthecxcl8cxcr12axisinthetumormicroenvironmentandimmunotherapy AT yangbingli rolesofthecxcl8cxcr12axisinthetumormicroenvironmentandimmunotherapy AT luxiyang rolesofthecxcl8cxcr12axisinthetumormicroenvironmentandimmunotherapy AT huijuancheng rolesofthecxcl8cxcr12axisinthetumormicroenvironmentandimmunotherapy AT xinliu rolesofthecxcl8cxcr12axisinthetumormicroenvironmentandimmunotherapy AT haochen rolesofthecxcl8cxcr12axisinthetumormicroenvironmentandimmunotherapy |