Toll‑like receptor agonist rMBP‑NAP enhances antitumor cytokines production and CTL activity of peripheral blood mononuclear cells from patients with lung cancer

Abstract

Toll-like receptor (TLR) agonists are known for their ability to inhibit tumor progression via enhancing antitumor cytokines production and cytotoxic T lymphocyte (CTL) activity. Recombinant Helicobacter pylori neutrophil-activating protein fused with maltose-binding protein (rMBP-NAP) has been reported as a novel TLR agonist for antitumor treatment in murine models. The present study aimed to determine the potential and efficacy of the rMBP-NAP for antitumor treatment prior to further clinical trials. The rMBP-NAP was expressed and purified for subsequent experiments. Peripheral blood mononuclear cells (PBMCs) from health donors and patients with lung cancer (LC) were incubated with PBS and 0.2 mg/ml rMBP-NAP. Antitumor cytokines production was assayed using ELISA and reverse transcription-quantitative polymerase chain reaction analysis. The cytolytic activity of PBMCs and the number of Interferon-γ (IFN-γ)-secreting cells were assayed using lactate dehydrogenase and Enzyme-linked ImmunoSpot assays, respectively. The results from the present study revealed that the expression of IFN-γ, interleukin (IL)-2, tumor necrosis factor-α and IL-12 of PBMCs from patients with LC and healthy donors were significantly increased following treatment with rMBP-NAP (P<0.05). Additionally, rMBP-NAP significantly upregulated the number of IFN-γ-secreting cells in PBMCs and prominently increased the cytotoxic activity of PBMCs (P<0.05). Furthermore, the expression of TLR2 was significantly enhanced following rMBP-NAP stimulation (P<0.05), which indicated that rMBP-NAP may serve an antitumor role via TLR2 signaling pathways. Overall, these results demonstrated that rMBP-NAP possesses the potential to be a novel immunomodulatory candidate drug and requires further evaluation in clinical trials.

The Immunotherapeutic Role of Type I and III Interferons in Melanoma and Non-Melanoma Skin Cancers

“…Cancer immunotherapy has rapidly advanced in recent years [ 21 ]. The main goal of cancer immunotherapy is to activate passive or active immunity to target tumors and combat growing malignancies [ 22 ]. Biologic agents such as antibodies, checkpoint inhibitors, and cytokines are a few of the many that comprise cancer immunotherapy [ 23 ].…”

“…The cancer immunity cycle refers to the cyclic process during which neoantigens produced by cancer cells are released after cell death, captured, and then presented to T cells by antigen-presenting cells, activating effector T cells [ 25 ]. Effector T cells then traffic and infiltrate tumor tissue, where they kill cancer cells with the same tumor antigens, causing more antigen release [ 22 ]. Several studies have revealed that IFN signaling plays a critical role in the success of cancer therapy strategies.…”

Neutrophil-activating protein in Bacillus spores inhibits casein allergy via TLR2 signaling

“…Moreover, NAP is currently being studied in tumor therapy given its ability to induce TLR2 transcripts and promote peripheral blood mononuclear cells of cancer patients to secrete IFN-γ and IL-12. [49][50][51][52][53] Once TLR2 signaling is activated, the bridging protein MYD88 activates the downstream factors NF-κB and transcription activator protein 1 (AP-1) to secrete cytokines such as IL-12. 54 Additionally, the transcriptional regulator c-JUN is an important element of the JAK/STAT pathway and a component of AP-1.…”

Effects of helicobacter pylori on tumor microenvironment and immunotherapy responses

“…This induces antitumor effects through a TLR-2-dependent mechanism in subcutaneous hepatoma and sarcoma mice model ( 156 ). rMBP-NAP can significantly increase peripheral blood mononuclear cells (PBMCs) that secrete IFN-γ, and prominently increases the cytotoxic activity of PBMCs derived from lung cancer patients ( 157 ). Treatment with rMBP-NAP restricts the progression of metastatic lung cancer in mice model by triggering antitumor immunity ( 158 ).…”