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Table 1 Effects of complement system on the TME and their therapeutic potential for cancer treatment

From: Role of the complement system in the tumor microenvironment

Complement proteinMalignancy types/modelsFunctions in the TMEExample dugsRefs.
C1qMelanoma (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 DCsNo correlational studies[23, 25, 27, 98]
C3aMelanoma (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 treatmentCompstatin (C3-targeted complement inhibitor)[13, 15, 58, 67, 77, 81]
C3dLymphoma (murine models and patient samples)Serve as a predictive biomarker for response to cancer treatment or the tumor stageNo correlational studies[121]
C4dOral squamous cell carcinoma (patient samples), lung cancer (patient samples)Serve as a diagnostic and prognostic biomarker for cancer progressionNo correlational studies[19, 20]
C5aLung 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-1Eculizumab (C3-targeted complement inhibitor)
PMX-53 (C5a/C5aR inhibition)
[17, 39, 44, 66, 73, 109]
C7Liver cancer (murine models, patient samples and cell lines)Promote the stemness of liver cancer cellsNo correlational studies[93]
mCRPsMany types of cancers (murine models, patient samples and cell lines)Protect cancer cells from MAC-mediated CDC and regulate the response of T cellsBispecific antibodies[39, 101, 103, 104]
MBL-MASPGlioblastoma 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 carcinomaNo correlational studies[112,113,114]
FBGlioblastoma multiforme (patient samples)Serum levels of FB were decreased in glioblastomaNo correlational studies[112]
FHLiver 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 cancerNo correlational studies[93, 94]