TABLE 1.
Preclinical Data Supporting Myeloid Cell–Targeted Therapy as Therapeutic Strategies in Solid Tumors
| Name | Target | Mechanism | Effective as Monotherapy? | Tumor Type | Antitumor Effects | Ref. |
|---|---|---|---|---|---|---|
| BLZ945 | CSF-1R inhibition | Repolarized MΦ to M1-like | Y | GBM | Blocked glioma progression and improved survival |
(Pyonteck, 38) |
| GW2580 | CSF-1R inhibition | TIM depletion | N: combined with radiotherapy |
Prostate | Enhanced radiation-induced suppression of tumor growth |
(Xu, 39) |
| PLX3397 | CSF-1R inhibition | Macrophage depletion enhanced antitumor CD8+ T cell–dependent chemotherapy cytotoxicity |
N: combined with paclitaxel |
PyMT mammary | Enhanced chemotherapy-induced slowing of tumor growth, reduced lung metastasis, and increased survival |
(DeNardo, 24) |
| BLZ945 | CSF-1R inhibition | Slowed TAM turnover, reduced macrophage recruitment, and increased CD8+ T cell tumor infiltration |
Y | PyMT mammary, HPV16 cervical |
Inhibited tumor growth | (Strachan, 34) |
| PLX3397 | CSF-1R inhibition | Reduced TIMs and skewed population of MΦ to MHC1Ihi |
N: combined with ACT |
Melanoma | Improved ACT and reduced tumor growth due to improved T cell effector function |
(Mok, 44) |
| GW2580 PLX3397 αCSF1 |
CSF-1/CSF-1R blockade |
Depleted TAMs, enhanced antigen presentation and induced T cell responses |
N: combined with PD-1 and CTLA4 antagonists |
PDAC | Enhanced checkpoint-based immunotherapies to limit PDAC progression |
(Zhu, 43) |
| GW2580 PLX3397 PF-04136309 |
CSF-1R inhibition + CCR2 inhibition |
Depleted TAMs and inflammatory monocytes |
N: combined with gemcitabine |
PDAC | TAM depletion enhanced response to chemotherapy and reduced metastasis via increased antitumor T cell responses |
(Mitchem, 41) |
| αCCL2 | CCL2/CCR2 signaling blockade |
Reduced PSA levels and slowed tumor growth in bone |
Y/N: antitumor effect greater when combined with docetaxel |
Prostate cancer growth in bone |
Enhanced docetaxel-mediated inhibition of prostate cancer cell growth in bone |
(Kirk, 126) |
| αCCL2 | CCL2/CCR2 signaling blockade |
Blocked inflammatory monocyte recruitment to metastatic sites |
Y | PyMT mammary | Reduced metastatic burden and increased survival |
(Qian, 27) |
| Ibrutinib | Btk | Enhanced antitumor CD8+ T cell-mediated immunity induced by checkpoint blockade |
N: combined with anti–PD-L1 therapy |
4T1 mammary, CT26 colon |
Enhanced anti–PD-L1–mediated reduction in tumor growth and metastasis; combination therapy induced long-term memory and blunted tumor regrowth in rechallenge studies |
(Sagiv-Barfi, 107) |
| PI-3065 | PI3Kδ | Reduced Treg population and increased tumor CD8+ T cell infiltration |
Y | 4T1 mammary, KPC pancreatic |
Suppressed tumor growth and metastasis | (Ali, 112) |
| TG100-115 AS605240 |
PI3Kγ | Inhibited integrin α4β1 activation; impaired myeloid/macrophage trafficking; reduced inflammation and angiogenesis |
Y | Lewis lung carcinoma, PyMT mammary |
Suppressed inflammation, angiogenesis, and tumor growth |
(Schmid, 127) |
ACT indicates adoptive cell therapy; Btk, Bruton tyrosine kinase; CCL2, chemokine (C-C motif) ligand 2; CCR2, C-C chemokine receptor type 2; CTLA4, cytotoxic T-lymphocyte—associated protein 4; GBM, glioblastoma multiforme; HPV, human papillomavirus; MΦ, macrophage; MHC II, major histocompatibility complex class II; PD-1, programmed death-1; PDAC, pancreatic ductal adenocarcinoma; PD-L1, programmed death ligand-1; PI3K, phosphatidylinositide 3-kinase; PSA, prostate-specific antigen; PyMT, polyoma middle T; TAM, tumor associated macrophage; Treg, regulatory T cell; TIM, tumor-infiltrating myeloid cell; Y, yes; N, no.