Targeting myeloid cells to improve cancer immune therapy
Tumor immunosuppression remains a major barrier to effective cancer immunotherapy and is often driven by the immunoregulatory activities of innate immune cells, such as myeloid cells within the tumor microenvironment (TME). Myeloid populations—including tumor-associated macrophages (TAMs), dendritic...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-07-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1623436/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849420826255818752 |
|---|---|
| author | Hui Chen Hui Chen Zihan Xu Judith Varner Judith Varner |
| author_facet | Hui Chen Hui Chen Zihan Xu Judith Varner Judith Varner |
| author_sort | Hui Chen |
| collection | DOAJ |
| description | Tumor immunosuppression remains a major barrier to effective cancer immunotherapy and is often driven by the immunoregulatory activities of innate immune cells, such as myeloid cells within the tumor microenvironment (TME). Myeloid populations—including tumor-associated macrophages (TAMs), dendritic cells, granulocytes, monocytes and myeloid-derived suppressor cells (MDSCs)—play pivotal roles in dampening anti-tumor immune responses and promoting tumor progression. Recent advances in our understanding of myeloid cell biology have unveiled new therapeutic opportunities to disrupt these immunosuppressive mechanisms associated with tumor inflammation. This review highlights key signaling pathways and surface molecules involved in myeloid-mediated immune suppression, including CSF1R, PI3Kγ, mTOR, Syk, MerTK/Axl, and immune checkpoints such as Trem2, LILRBs, VISTA, and CD40. We examine preclinical and clinical findings that support targeting these pathways to reprogram the TME and enhance anti-tumor immunity. By integrating insights from mechanistic studies and therapeutic development, this review underscores the potential of myeloid cell-targeting strategies as promising adjuncts to current cancer immunotherapies. Finally, we discuss future directions and challenges in translating these approaches into durable clinical benefit. |
| format | Article |
| id | doaj-art-c44cd76e66e841b48559a4137d2ffb4e |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-c44cd76e66e841b48559a4137d2ffb4e2025-08-20T03:31:38ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.16234361623436Targeting myeloid cells to improve cancer immune therapyHui Chen0Hui Chen1Zihan Xu2Judith Varner3Judith Varner4Moores Cancer Center, University of California, San Diego, La Jolla, CA, United StatesDepartment of Pathology, University of California, San Diego, La Jolla, CA, United StatesMoores Cancer Center, University of California, San Diego, La Jolla, CA, United StatesMoores Cancer Center, University of California, San Diego, La Jolla, CA, United StatesDepartment of Pathology, University of California, San Diego, La Jolla, CA, United StatesTumor immunosuppression remains a major barrier to effective cancer immunotherapy and is often driven by the immunoregulatory activities of innate immune cells, such as myeloid cells within the tumor microenvironment (TME). Myeloid populations—including tumor-associated macrophages (TAMs), dendritic cells, granulocytes, monocytes and myeloid-derived suppressor cells (MDSCs)—play pivotal roles in dampening anti-tumor immune responses and promoting tumor progression. Recent advances in our understanding of myeloid cell biology have unveiled new therapeutic opportunities to disrupt these immunosuppressive mechanisms associated with tumor inflammation. This review highlights key signaling pathways and surface molecules involved in myeloid-mediated immune suppression, including CSF1R, PI3Kγ, mTOR, Syk, MerTK/Axl, and immune checkpoints such as Trem2, LILRBs, VISTA, and CD40. We examine preclinical and clinical findings that support targeting these pathways to reprogram the TME and enhance anti-tumor immunity. By integrating insights from mechanistic studies and therapeutic development, this review underscores the potential of myeloid cell-targeting strategies as promising adjuncts to current cancer immunotherapies. Finally, we discuss future directions and challenges in translating these approaches into durable clinical benefit.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1623436/fullmyeloid celltumor associated macrophage (TAM)PI3KgammaTREM2CSF1R (colony stimulating factor 1 receptor)Axl |
| spellingShingle | Hui Chen Hui Chen Zihan Xu Judith Varner Judith Varner Targeting myeloid cells to improve cancer immune therapy Frontiers in Immunology myeloid cell tumor associated macrophage (TAM) PI3Kgamma TREM2 CSF1R (colony stimulating factor 1 receptor) Axl |
| title | Targeting myeloid cells to improve cancer immune therapy |
| title_full | Targeting myeloid cells to improve cancer immune therapy |
| title_fullStr | Targeting myeloid cells to improve cancer immune therapy |
| title_full_unstemmed | Targeting myeloid cells to improve cancer immune therapy |
| title_short | Targeting myeloid cells to improve cancer immune therapy |
| title_sort | targeting myeloid cells to improve cancer immune therapy |
| topic | myeloid cell tumor associated macrophage (TAM) PI3Kgamma TREM2 CSF1R (colony stimulating factor 1 receptor) Axl |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1623436/full |
| work_keys_str_mv | AT huichen targetingmyeloidcellstoimprovecancerimmunetherapy AT huichen targetingmyeloidcellstoimprovecancerimmunetherapy AT zihanxu targetingmyeloidcellstoimprovecancerimmunetherapy AT judithvarner targetingmyeloidcellstoimprovecancerimmunetherapy AT judithvarner targetingmyeloidcellstoimprovecancerimmunetherapy |