Posted on October 10, 2025

On September 10, Nature published online the article “Myeloid progenitor dysregulation fuels immunosuppressive macrophages in tumours, marking the 10th Nature/Science/Cell paper in 2025 featuring Bio X Cell’s CSF1R antibody (clone AFS98).

In recent years, dissecting the role of myeloid cells, especially monocyte-macrophage, in the tumor microenvironment (TME) and exploring therapeutic approaches targeting these populations has become a major research focus. Here, we review the latest oncology progress powered by Bio X Cell’s anti-CSF1R antibodies.

Macrophages Mediate Adoptive T Cell Clearance in the TME (Nature, 2024)

The authors examined anti-CD47 antibodies in combination with adoptive T cells. Surprisingly, rather than enhancing anti-tumor efficacy, the addition of anti-CD47 abrogated the therapeutic benefit of CAR-T/TCR-T cells.

The mechanism was that infused CAR-T/TCR-T cells recruited macrophages into tumors. Adoptive T cells express relatively low levels of CD47, adding anti-CD47 further reduced the “don’t eat me” signal, resulting in rapid and potent T cell ablation. When macrophages were depleted, however, CAR-T cells persisted, even in the presence of anti-CD47. This confirmed that anti-CD47 induced macrophage-mediated phagocytosis of CAR-T cells.

To overcome this challenge, the authors engineered adoptive T cells expressing a CD47 variant (Q31P) that engaged SIRP? but was not blocked by anti-CD47 antibodies. When combined with anti-CD47, these engineered T cells exhibited enhanced anti-tumor efficacy.

In this study, macrophage depletion was achieved using a combination of clodronate liposomes (200 μl, intravenous) and Bio X Cell’s anti-CSF1R (400 μg, intraperitoneal) during pre-treatment, followed by maintenance dosing of 400 μg of anti-CSF1R three times per week throughout the experiment.

Dysregulated Myeloid Progenitors Fuel Immunosuppressive Macrophages (Nature, 2025)

Monocyte-derived macrophages (mo-macs) often drive immunosuppression in the TME, and tumors enhance myelopoiesis in the bone marrow fuels these populations.

The latest Nature study performed paired transcriptome and chromatin accessibility profiling in NSCLC patient samples and mouse models. It showed Nfe2l2 (NRF2) as a key transcriptional regulator driving epigenetic reprogramming of myeloid progenitors.

NRF2 genetic deletion and pharmacological inhibition significantly reduced the survival and immunosuppression of mo-macs in TME, restoring NK and T cell anti-tumor immunity and enhancing checkpoint blockade efficacy.

In a KrasLSL-GDD2/+;Trp53fl/fl lung cancer model, administration of Bio X Cell’s anti-CSF1R antibody (400 μg, every other day) effectively depleted monocytes and macrophages. Tumor burden was clearly reduced in NRF2-proficient mice, but not in NRF2-deficient mice, suggesting NRF2 activation in mo-macs is crucial to orchestrating immunosuppression.

Synergy with CAR-T Cell Therapy in Aggressive B-Cell Lymphoma (Cancer Cell, 2025)

The study aimed to elaborate CAR-T resistance in relapsed or refractory aggressive B-cell lymphoma from a TME perspective. The authors performed high-dimensional analyses including single-cell RNA sequencing, imaging mass cytometry, and MACSima imaging cycle staining in durable and non-durable responding CAR-T cell patients and identified a distinct CSF1R⁺CD14⁺CD68⁺ lymphoma-associated myeloid-monocytic (LAMM) cell population. These cells inhibit CAR-T cell function and correlate with poor outcome.

In a fully immunocompetent, autochthonous DLBCL mouse model, CSF1R inhibition displayed synergistic treatment effects in combination with CD19 CAR-T cells. For in vivo CSF1R inhibition, mice were treated three times per week with Bio X Cell’s anti-CSF1R antibody at 400 μg per dose (16 mg/kg body weight) via intraperitoneal injection. Treatment started on day -2 until day 28 post-CAR-T cell infusion. LAMM cell depletion was confirmed at both the transcriptional and protein levels. Compared to CAR-T alone, the addition of the anti-CSF-1R antibody significantly improved PFS and the number of durable responders with long-lasting, complete remissions, which resulted in a significantly prolonged OS.

Csf1r Low-expressing TAMs Drive Resistance in Prostate Cancer (Nature, 2025)

Despite encouraging results in several studies, CSF1R blockade was clinically ineffective in metastatic castration-resistant prostate cancer (mCRPC). The study identified a distinct immunosuppressive population of tumor-associated macrophages with elevated levels of SPP1 transcripts (SPP1hi-TAMs) in both patient biopsies and syngeneic mouse models. These cells expressed low Csf1r, making them not responsive to anti-CSF1R antibody treatment.

To determine whether SPP1hi-TAMs are resistant to CSF1R blockade, mice were randomly divided into two groups when they developed CRPC (tumor volume of 100-200 mm3) and were administered intraperitoneally 1 mg Bio X Cell’s anti-CSF1R antibody or isotype control, followed by a 0.5 mg maintenance dose after 5 days. Flow cytometry 2 days after the final injection showed that macrophages with high expression of Csf1r transcripts, including CD163hi-TAMs and CX3CR1hi-TAMs, were significantly ablated, but SPP1hi-TAMs remained largely unaffected.

Further analysis suggested adenosine signaling as a potential mechanism for SPP1hi-TAMs-mediated immunotherapeutic resistance. Combining ciforadenant (adenosine A2A receptor inhibitor) with atezolizumab (anti-PD-L1) induced clinical responses in mCRPC patients.

These recent CSF1R studies highlight the pivotal role of macrophages in regulating tumor immunity and immunotherapy responses. With tools like Bio X Cell’s CSF1R antibodies, researchers can dissect the heterogeneity of myeloid populations in the TME, accelerate mechanistic insights, and develop strategies to overcome resistance in immunotherapy.

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