FOLFOX regimen plus dendritic cells–cytokine-induced killer cells immunotherapy for the treatment of colorectal cancer: a meta-analysis

Abstract

PurposeTo systematically investigate the efficacy and safety of the combination of FOLFOX (oxaliplatin, 5-fluorouracil, and leucovorin) regimen and cocultured dendritic cells and cytokine-induced killer cells (DC-CIK) immunotherapy for the treatment of colorectal cancer (CRC).MethodsPublications reporting the clinical trials’ responses or safety of FOLFOX regimen combined with DC-CIK immunotherapy in treating CRC patients were searched in PubMed, Embase, Cochrane Library, China National Knowledge Internet, and Wanfang databases. Trials meeting the selection criteria were analyzed. The overall survival (OS), overall response rate (ORR), disease control rate (DCR), tumor markers, immune function, and adverse events were evaluated.ResultsTen trials including 881 CRC patients were analyzed in this meta-analysis. The combined therapy showed advantages over FOLFOX treatment-alone in 2-year OS (odds ratio [OR] =2.77, confidence interval [CI] =1.58–4.86, P=0.0004), ORR (OR =1.85, CI =1.34–2.56, P=0.0002), and DCR (OR =2.54, CI =1.76–3.67, P<0.00001), with statistical significance. After immunotherapy, lymphocyte subset percentages of CD3+ (P=0.0006) and CD4+ (P=0.01), CD4+/CD8+ ratio (P=0.0003), and levels of cytokines IFN-γ (P=0.003) and IL-2 (P=0.01) were significantly increased, whereas analysis of CD8+, CD3−CD56+, CD3+CD56+, CD4+CD25+, IL-6, and TNF-α did not show any significant difference (P>0.05). Moreover, the level of carcinoembryonic antigen was also decreased significantly upon immunotherapy (P<0.00001).ConclusionThe combination of FOLFOX regimen and DC-CIK immunotherapy was safe and effective for CRC patients.

Bacterial ghosts as adjuvant to oxaliplatin chemotherapy in colorectal carcinomatosis

“…60 Accordingly, there is already clinical evidence that by stimulating dendritic cells (and also NK cells) via in vitro cytokine treatment, the anti-CRC activity of the FOLFOX scheme can be improved. 61 The mechanism of DC activation by BGs, via PAMPs, relies on direct induction of PRR signalling (e.g. TLR 4), which are generally found on antigen-presenting cells.…”

Retrospective analysis of the efficacy of cytokine‐induced killer cell immunotherapy combined with first‐line chemotherapy in patients with metastatic colorectal cancer

“…Moreover, our previous studies demonstrated the feasibility and low toxicity of CIK cell treatment for several kinds of cancer, including hepatocellular carcinoma, breast cancer, epithelial ovarian cancer, non‐small‐cell lung cancer and nasopharyngeal carcinoma . Other studies reported the effectiveness of dendritic cell (DC)–CIK/CIK immunotherapy for colorectal cancer . However, the therapeutic efficacy of CIK cell treatment for patients with mCRC is poorly understood and needs further confirmation.…”

“…In some situations, cell‐based immunotherapy offers a valuable and more effective alternative to conventional cytotoxic therapy . A series of studies have demonstrated the efficacy of adoptive cell immunotherapy, including tumor‐infiltrating lymphocytes, antigen‐specific T lymphocytes, cytokine‐induced killer (CIK) cells and chimeric antigen receptor (CAR) T cells . Among them, CIK cells have characteristics of rapid proliferation, strong antitumor activity, broad spectrum of antitumor activity and minimal toxicity and have been demonstrated as effective in many tumors, including CRC .…”

“…4,7 A series of studies have demonstrated the efficacy of adoptive cell immunotherapy, including tumorinfiltrating lymphocytes, antigen-specific T lymphocytes, cytokine-induced killer (CIK) cells and chimeric antigen receptor (CAR) T cells. [8][9][10][11] Among them, CIK cells have characteristics of rapid proliferation, strong antitumor activity, broad spectrum of antitumor activity and minimal toxicity and have been demonstrated as effective in many tumors, 12 including CRC. 11,[13][14][15] Moreover, our previous studies demonstrated the feasibility and low toxicity of CIK cell treatment for several kinds of cancer, including hepatocellular carcinoma, 16 breast cancer, 17,18 epithelial ovarian cancer, 19 non-small-cell lung cancer 20 and nasopharyngeal carcinoma.…”

“…21 Other studies reported the effectiveness of dendritic cell (DC)-CIK/CIK immunotherapy for colorectal cancer. 11,[13][14][15] However, the therapeutic efficacy of CIK cell treatment for patients with mCRC is poorly understood and needs further confirmation.…”