Table 1.

Effects of complement system on the TME and their therapeutic potential for cancer treatment

Complement protein	Malignancy types/models	Functions in the TME	Example dugs	Refs.
C1q	Melanoma (murine models and cell lines), cervical cancer (murine models), breast cancer (cell lines), pancreatic cancer (cell lines), colon cancer (cell lines) and lung cancer (cell lines)	Promote angiogenesis, cell adhesion, proliferation and metastasis independent of complement activation, and inhibit the inflammatory response of macrophages and DCs	No correlational studies	[23, 25, 27, 98]
C3a	Melanoma (murine models, patient samples and cell lines), lung cancer (murine models, patient samples and cell lines), gastric cancer (murine models, patient samples and cell lines), colon cancer (murine models, patient samples and cell lines), breast cancer (patient samples and cell lines), pancreatic cancer (patient samples and cell lines)	Promote tumor growth, metastasis, EMT and angiogenesis; regulate the function of TAMs, MDSCs, DCs and Tregs; and serve as a predictive biomarker for cancer diagnosis and response to cancer treatment	Compstatin (C3-targeted complement inhibitor)	[13, 15, 58, 67, 77, 81]
C3d	Lymphoma (murine models and patient samples)	Serve as a predictive biomarker for response to cancer treatment or the tumor stage	No correlational studies	[121]
C4d	Oral squamous cell carcinoma (patient samples), lung cancer (patient samples)	Serve as a diagnostic and prognostic biomarker for cancer progression	No correlational studies	[19, 20]
C5a	Lung cancer (murine models, patient samples and cell lines), gastric cancer (murine models, patient samples and cell lines), hepatocellular carcinoma (murine models and cell lines), colorectal cancer (murine models and cell lines), breast cancer (murine models and cell lines), ovarian cancer (murine models and cell lines), melanoma (murine models), ovarian cancer (murine models), cervical cancer (murine models)	Promote tumorigenesis, tumor growth, angiogenesis, cell motility and invasiveness and inhibit immune function by inducing MDSCs or decreasing CD8+ T cells. Blockade of C5aR significantly reduced MDSCs and the immunomodulators ARG1, CTLA-4, IL-6, IL-10, LAG3, and PDL-1	Eculizumab (C3-targeted complement inhibitor) PMX-53 (C5a/C5aR inhibition)	[17, 39, 44, 66, 73, 109]
C7	Liver cancer (murine models, patient samples and cell lines)	Promote the stemness of liver cancer cells	No correlational studies	[93]
mCRPs	Many types of cancers (murine models, patient samples and cell lines)	Protect cancer cells from MAC-mediated CDC and regulate the response of T cells	Bispecific antibodies	[39, 101, 103, 104]
MBL-MASP	Glioblastoma multiforme (patient samples), colorectal cancer (patient samples), hepatocellular carcinoma (murine models)	Protect against the initiation and progression of glioblastoma and colorectal cancer, while suppressing the growth of hepatocellular carcinoma	No correlational studies	[112–114]
FB	Glioblastoma multiforme (patient samples)	Serum levels of FB were decreased in glioblastoma	No correlational studies	[112]
FH	Liver cancer (murine models, patient samples and cell lines), cutaneous squamous cell cancer (patient samples and cell lines)	Promote the stemness of liver cancer cells and serve as a biomarker for the tumor progression of cutaneous squamous cell cancer	No correlational studies	[93, 94]