Complement in Cancer and Cancer Immunotherapy

Kolev, Martin; Towner, Laurence; Donev, Rossen

doi:10.1007/s00005-011-0146-x

Cited by 63 publications

(69 citation statements)

References 131 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Since the activation of complement cascade may lead not only to CDC mediated cell death, but also plays an important role in the enhancement of the ADCC and the adaptive immune response via the release of complement activation products, such as C5a and C3a (6,23,31,34,48,60). Thus we speculate that the expression of CD55 may further inhibit the antitumor immune response by affecting ADCC and the adaptive immune response in vivo.…”

Section: Discussionmentioning

confidence: 86%

CD55 limits sensitivity to complement-dependent cytolysis triggered by heterologous expression of α-gal xenoantigen in colon tumor cells

Wang

Qin

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

Y. CD55 limits sensitivity to complement-dependent cytolysis triggered by heterologous expression of ␣-gal xenoantigen in colon tumor cells. Am J Physiol Gastrointest Liver Physiol 306: G1056-G1064, 2014. First published April 24, 2014 doi:10.1152/ajpgi.00464.2013.-Engineering cancer cells to express heterologous antigen ␣-gal and induce the destruction of tumor cells depending on the complement cascade may be a promising strategy of tumor therapy. However, the feasibility and effect of using ␣-gal to induce colorectal adenocarcinoma cell line cytolysis is not yet known. In this study, we evaluated ␣-gal expression's ability to sensitize human colorectal adenocarcinoma cell lines to complement attack in cell lines LoVo, SW620, and Ls-174T. Nearly all ␣-gal-expressing LoVo and SW620 cells were killed by normal human serum (NHS), but ␣-gal-expressing Ls-174T cells showed no significant lysis. We analyzed the expression levels of membrane-bound complement regulatory proteins (mCRPs) on the three cell lines, and their protective role in ␣-gal-mediated activation of the complement. LoVo showed no expression of any of the three proteins. CD59 was strongly expressed by SW620 and Ls-174T. CD46 and CD55 varied between the two cell lines. CD46 on SW620 was only half the intensity of CD46 on Ls-174T. Ls-174T showed a notable expression of CD55, while expression of CD55 on SW620 was not detected. The sensitivity of Ls-174T expressing ␣-gal to NHS greatly increased following the downregulation of CD46 and CD55 with short hairpin RNA (shRNA). However, there is no increase in cell killing when CD59 expression was diminished. Our findings suggest that the use of ␣-gal as antigen to induce tumor cell killing may be a potential therapeutic strategy in colon cancer and that CD55 plays a primary role in conferring resistance to lysis. ␣-gal epitope; membrane-bound complement regulatory proteins; complement-dependent cytotoxicity; colorectal carcinoma COLORECTAL CANCER is the third most commonly diagnosed cancer in males and the second in females (28, 57). Surgery is the mainstay of treatment in most cases of colon cancer. Adjuvant therapies, primarily chemotherapy and radiotherapy, have improved the survival rate and quality of life in colorectal cancer patients. However, the 5-yr survival rate remains at ϳ50%, which explains the growing interest in alternative therapies that have no serious side effects and that have the potential to eradicate residual tumors after conventional treatment. A deeper understanding of the interaction between the host immune system and malignant tumors has enabled the development of effective clinical strategies that improve immune responses against tumors. We seek to develop a therapeutic strategy that induces a specific immune response resulting in direct tumor cell killing, depending on the activation of the complement system.

show abstract

Section: Discussionmentioning

confidence: 86%

CD55 limits sensitivity to complement-dependent cytolysis triggered by heterologous expression of α-gal xenoantigen in colon tumor cells

Wang

Qin

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

show abstract

“…Secretion of C3-degrading or C9-phosphorylated enzymes, overexpression of complement-inhibitory proteins, removal of the MAC complex from the surface and reduction of C6 and C7 expression levels in tumor tissues were reported to help the tumor escape complement-dependent cytotoxicity. 19,27,28 In terms of liver cells, increasing the expression levels of CD46 and CD59 seem to be somehow decisive in protecting hepatocytes against complement lysis. 29,30 As shown above, recipient rs9200 GA type had relatively higher recurrence risk, lower RFS and reduced OS.…”

Section: Discussionmentioning

confidence: 99%

Recipient C6 rs9200 genotype is associated with hepatocellular carcinoma recurrence after orthotopic liver transplantation in a Han Chinese population

Wang

Liao

et al. 2016

Cancer Gene Ther

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) recurrence is one of the leading causes of death after orthotopic liver transplantation (OLT). The sixth complement component (C6) is a late-acting complement protein that participates in the assembly of the membrane attack complex, which has an indispensable role in innate and acquired immune responses, as well as cancer immune surveillance. However, studies assessing the association between C6 and HCC recurrence after OLT are scarce. This study aimed to evaluate the association of donor and recipient C6 single-nucleotide polymorphisms with the risk for HCC recurrence after OLT. A total of 71 adult patients who underwent primary LT for HCC were enrolled. HCC recurrence was observed in 26 (36.6%) patients. Ten single-nucleotide polymorphisms were genotyped and analyzed in both donor and recipient groups. Patients with the rs9200 heterozygous GA variant presented significantly higher HCC recurrence rates (54.17 vs 27.66%, P=0.028), and lower cumulative tumor-free survival and overall survival (P=0.006 and P=0.013, respectively) compared with those harboring the GG/AA genotype, in multivariate logistic regression and Cox regression analyses. The rs9200 heterozygous GA variant in C6 persisted as a statistically independent prognostic factor (P<0.05) for predicting HCC recurrence after OLT. In conclusion, recipient C6 rs9200 polymorphism is associated with HCC recurrence after OLT, and improves the predictive value of clinical models.

show abstract

“…Neutralization of CD59 with an anti-CD59 monoclonal antibody or inhibition of cd59 expression by siRNA significantly enhances CDC of the ovarian cell lines (Kolev et al, 2011). Prognosis Significant reduced levels of CD59 were detected in the urine of patients with ovarian carcinoma compared to the control subjects (Abdullah-Soheimi et al, 2010).…”

Section: Ovarian Cancermentioning

confidence: 99%