Table 3.

Ongoing clinical trials targeting TAMCs

Strategies	Class	Treatment	Conditions	With ICBs or not	Outcomes	Adverse effects
Blocking expansion and recruitment of TAMCs	CCR2 inhibitor	PF-04136309, MLN1202, BMS-813160, etc	Pancreatic ductal adenocarcinoma, melanoma, metastatic cancer, etc	Both monotherapy and synergistic ICBs are available	ORR was 16.7–49%. About 33% of patients had reduced metastasis markers. But some trials have been stopped for lack of clinical benefit	Fatigue and anemia were common. DLTs were present. Neutropenia may occur with concurrent chemotherapy
	VEGFR inhibitor	Axitinib, Cabozantinib, Pazopanib, etc	Renal cell carcinoma, breast cancer, small cell lung cancer, etc	Both monotherapy and synergistic ICBs are available	OS and PFS were significantly prolonged, and ORR was increased	The incidence rate of serious AEs was about 40%. The most common AE was diarrhea
	CSF1R inhibitor	Cabiralizumab, PLX3397, ARRY-382, etc	Advanced solid tumor, melanoma, non-small cell lung cancer, etc	Mostly in collaboration with ICBs	The objective response rate was 0–16.7%. PFS did not prolong significantly	The incidence rate of serious AEs and DLTs was 0–54.5%. Gastrointestinal diseases were common
Mitigating the immunosuppressive ability of TAMCs	COX-2 inhibitor	Celecoxib, apricoxib, etc	Breast cancer, non-small cell lung cancer, etc	Collaboration with ICBs is rare	PFS did not significantly prolong or even shorten. There was no clinical benefit	The incidence rate of serious AEs was similar to that of placebo group
	PDE5 inhibitor	Tadalafil, Sildenafil, etc	Head and neck squamous cell carcinoma, prostatic neoplasms, etc	No	The activity of Arg-1 and iNOS was significantly decreased, reversing tumor specific immune suppression	No AEs are reported
	TLR agonist	CMP-001, Imiquimod, SD-101, etc	Melanoma, head and neck cancer, breast cancer, etc	Mostly in collaboration with ICBs	ORR was 0–55.6%, and progressive disease accounted for 11.1–44.4%. MPR also showed a mix of good and bad outcomes	The incidence rate of serious AEs was 16.67–44.4%. Chills and fatigue were prominent
Direct depletion	VEGFR inhibitor	Sunitinib malate, ZD6474, Apatinib, etc	Renal cell carcinoma, bladder cancer, breast cancer, gastric cancer, etc	Both monotherapy and synergistic ICBs are available	PFS and OS were prolonged in most trials. Some studies have shown that MDSC mediated immunosuppression is reversed	The incidence rate of serious AEs was 6.67–40%. Leukocytes and platelets were often affected
	C-kit inhibitor	Imatinib, Masitinib, Dasatinib, Dovitinib, etc	Salivary gland neoplasm, non-small cell lung cancer, melanoma, thyroid cancer, etc	Collaboration with ICBs is rare	Clinical benefit was limited. PFS was prolonged in some trials, but the results of some trials were mainly progressive disease	The incidence rate of serious AEs was 2.44–65%. Among them, diarrhea, nausea and vomiting were easy to occur
	Chemo therapy	Cisplatin, 5-FU, Carboplatin, Paclitaxel, Doxorubicin, etc	Esophageal neoplasms, breast cancer, non-small cell lung cancer, ovarian cancer, sarcoma, etc	Both monotherapy and synergistic ICBs are available	Effectiveness varies greatly depending on tumor type, drug dose, combination therapy, etc. Both trials with significant clinical benefit and trials with low ORR exist	Nausea, constipation and diarrhea were prominent in AEs. The hematopoietic system such as neutrophils and platelets were susceptible

ORR objective response rate, DLT dose limiting toxicities, OS overall survival, PFS progression-free survival, AE adverse event, MPR major pathologic response