Editorial: Advances in myeloid cell targeting for overcoming tumor immunosuppression

Dehong Yan^1*Qiong Yang^2*Jingying Zhou^3*

• ¹Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences (CAS), Shenzhen, China
• ²South China University of Technology School of Medicine, Guangzhou, China
• ³The Chinese University of Hong Kong, Hong Kong, Hong Kong, SAR China

Peng et al. developed a noninvasive iMRS using preoperative CT radiomics to predict the myeloid immune contexture in hepatocellular carcinoma (HCC). A multi-phase CT radiomics signature accurately predicted the pathological MRS, which reflects the balance of pro-and anti-tumor myeloid cells. A high iMRS was significantly associated with poor post-surgical overall and recurrence-free survival. Furthermore, in an immunotherapy cohort, a high iMRS predicted a better objective response and improved survival for patients treated with anti-PD-1/PD-L1 therapy, demonstrating its value as a noninvasive biomarker for prognosis and immunotherapy benefit assessment.The review by Chen et al. summarizes the potential of targeting myeloid cells to overcome immunosuppression in the tumor microenvironment (TME) and enhance cancer immunotherapy. Myeloid populations-such as TAMs, MDSCs, and tumor-associated dendritic cells-promote immune evasion through cytokine secretion, metabolic reprogramming, immune checkpoint expression, and physical exclusion of T cells. The article highlights key therapeutic targets, including CSF1R, PI3Kγ, mTOR, Syk, MerTK/Axl, and immune checkpoints like TREM2, LILRBs, VISTA, and CD40.Preclinical and clinical evidence supports strategies to deplete or reprogram these cells, restoring anti-tumor immunity.Combining myeloid-targeted agents with checkpoint inhibitors, chemotherapy, or radiation shows synergistic promise.However, challenges such as myeloid plasticity, toxicity, and biomarker development remain. Future success hinges on personalized approaches and rational combination therapies.Future research directions in targeting myeloid cells to overcome tumor immunosuppression will focus on several key areas. A major priority is the development of more selective agents and delivery systems, such as nanoparticles or bispecific antibodies, to precisely modulate specific myeloid subpopulations like TAMs or MDSCs without systemic toxicity. Understanding and targeting the metabolic and epigenetic reprogramming that sustains the immunosuppressive functions of these cells represent another critical avenue. Furthermore, identifying robust predictive biomarkers-through single-cell sequencing or spatial transcriptomics-is essential for patient stratification and for monitoring therapy-induced changes in the myeloid compartment in real-time. Finally, a central challenge is the rational design of combination therapies. This involves integrating myeloid-targeting agents with existing immunotherapies (e.g., checkpoint inhibitors, CAR-T), conventional treatments, or novel modalities like STING agonists to achieve synergistic efficacy, reverse resistance, and create a durable anti-tumor immune response in a wider range of cancers.