P. aeruginosa Mediated Necroptosis in Mouse Tumor Cells Induces Long-Lasting Systemic Antitumor Immunity

Qi, Jialong; He, Ju-Liang; Jin, Sun; Xu, Yang; Bai, Hongmei; Liu, Cun-Bao; Ma, Yanbing

doi:10.3389/fonc.2020.610651

Cited by 5 publications

(6 citation statements)

References 45 publications

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“…Furthermore, L. interrogans was observed on the surface of neutrophils and not phagocytized whereas L. biflexa was phagocytized ( 26 ) which further shows the importance of these cells in clearance of Leptospira . Here we show that apoptosis and necroptosis of neutrophils only in L. interrogans infected mice suggests that early removal of these cells from the innate immune cell repertoire and the enhanced inflammation promoted by necroptosis ( 29 ) may contribute to L. interrogans evasion, dissemination, pathogenesis and activation of the adaptive immune system characteristic of acute leptospirosis. We speculate that necroptosis may play a role in phagocytosis impairment by neutrophils in the presence of L. interrogans .…”

Section: Discussionmentioning

confidence: 85%

“…The increased expression of the active phosphorylated forms p-MLKL, p-RIP1 and p-RIP3 after pathogenic infection activates the necroptotic complex necessary to initiate the membrane pore formation in those immune cells to release inflammatory arsenals (DAMPs) necessary to maintain an inflammatory milieu and thereby invite the adaptive response which results in aggravated pathogenicity ( 12 ). These biomarkers were also increased in spleen cell lysates stimulated with other pathogens ( 5 , 17 , 29 , 32 ). The spotty increased expression of those key biomarkers at 24h and 72h post infection with the nonpathogenic L. biflexa suggests a discontinuous inflammatory process as the innate response is enough to provide protection.…”

Section: Discussionmentioning

confidence: 92%

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Necroptosis Contributes to Persistent Inflammation During Acute Leptospirosis

2022

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Leptospirosis is an emerging infectious disease. Recently, canine and human leptospirosis outbreaks were reported in California and New York, respectively. In this study we evaluated the role that cell death processes play in the inflammatory response to Leptospira. Groups of male C3H/HeJ mice were infected with pathogenic L. interrogans and non-pathogenic L. biflexa for 24 and 72 hours; inflammatory processes were characterized for apoptosis and necroptosis by flowcytometry of spleen cells and were further assessed for expression of biomarkers of necroptosis by western blot. We found that pathogenic L. interrogans promotes apoptosis in myeloid neutrophils and monocytes at 24h and 72h post-infection, whereas L. biflexa promotes apoptosis of myeloid monocytes only at 24h post-infection. It is interesting that the immune cells undergoing the common programmed cell death pathway (apoptosis) are the cell types which were not increased in frequency in spleen of mice infected with L. interrogans (neutrophils) and L. biflexa (monocytes) in our previous study. The same trend was observed with pathogenic L. interrogans inducing necroptosis of myeloid neutrophils in addition to monocytes and macrophages at 24h and/or 72h post-infection, whereas L. biflexa promoted this pro-inflammatory cell death process in monocytes and macrophages only at 24h post-infection. Thus, early apoptosis and necroptosis of these cell types may explain its absence in frequency in spleen. Furthermore, at 24h and 72h, expression of the necroptosis molecular biomarkers p-MLKL, p-RIP1 and p-RIP3 was increased post infection with pathogenic L. interrogans. These data suggest that the underlying cell death processes involved in immune responses to pathogenic Leptospira contribute directly to persistent inflammation during the early stages of leptospirosis.

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Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 92%

Necroptosis Contributes to Persistent Inflammation During Acute Leptospirosis

2022

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“…88 Pseudomonas aeruginosa can trigger robust and durable anti-tumor response by promoting tumor cell death with the secretion of HMGB-1, thereby stimulating DC maturation via TLR4/myD88 signaling and eliciting a longlasting anti-tumor immunity. 89 Additionally, peptidoglycan derived from Lactobacillus paracasei subp. paracasei X12 could induce ICD in colon cancer cell model through the release of HMGB1 and translocation of CRT.…”

Section: Bacteria or Microbial Metabolites Involved In Icd-related Ca...mentioning

confidence: 99%

Microbes mediated immunogenic cell death in cancer immunotherapy

Huang

Duan

Xie

et al. 2023

Immunological Reviews

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SummaryImmunogenic cell death (ICD) is one of the 12 distinct cell death forms, which can trigger immune system to fight against cancer cells. During ICD, a number of cellular changes occur that can stimulate an immune response, including the release of molecules called damage‐associated molecular patterns (DAMPs), signaling to immune cells to recognize and attack cancer cells. By virtue of their pivotal role in immune surveillance, ICD‐based drug development has been a new approach to explore novel therapeutic combinations and personalized strategies in cancer therapy. Several small molecules and microbes can induce ICD‐relevant signals and cause cancer cell death. In this review, we highlighted the role of microbe‐mediate ICD in cancer immunotherapy and described the mechanisms through which microbes might serve as ICD inducers in cancer treatment. We also discussed current attempts to combine microbes with chemotherapy regimens or immune checkpoint inhibitors (ICIs) in the treatment of cancer patients. We surmise that manipulation of microbes may guide personalized therapeutic interventions to facilitate anticancer immune response.

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“…In addition to PA-MSHA, the anti-tumor effects of a clinical isolate of P. aeruginosa strain 1409 were examined in vitro and in vivo by Qi et al. ( 20 ). The authors demonstrated that P. aeruginosa 1409 induced a programmed necrosis (necroptosis) of TC-1 tumor cells through activation of TLR4-RIP3-MLKL, and the HMGB1 released by the dying tumor cells further induced DC maturation and migration to tumor sites.…”

Section: Live Attenuated or Inactivated P Aeruginosa ...mentioning

confidence: 99%

“…The authors demonstrated that P. aeruginosa 1409 induced a programmed necrosis (necroptosis) of TC-1 tumor cells through activation of TLR4-RIP3-MLKL, and the HMGB1 released by the dying tumor cells further induced DC maturation and migration to tumor sites. Subsequently, the mature DC promoted T-cell responses by presenting tumor-associated antigens, thus resulting in remarkable tumor suppression in a TC-1 grafted tumor mouse model ( 20 ). This study indicates that the pathogenic clinical strains of P. aeruginosa could induce a potent anti-tumor response by reshaping tumor microenvironment.…”

Section: Live Attenuated or Inactivated P Aeruginosa ...mentioning

confidence: 99%

Pseudomonas aeruginosa in Cancer Therapy: Current Knowledge, Challenges and Future Perspectives

2022

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Drug resistance, undesirable toxicity and lack of selectivity are the major challenges of conventional cancer therapies, which cause poor clinical outcomes and high mortality in many cancer patients. Development of alternative cancer therapeutics are highly required for the patients who are resistant to the conventional cancer therapies, including radiotherapy and chemotherapy. The success of a new cancer therapy depends on its high specificity to cancer cells and low toxicity to normal cells. Utilization of bacteria has emerged as a promising strategy for cancer treatment. Attenuated or genetically modified bacteria were used to inhibit tumor growth, modulate host immunity, or deliver anti-tumor agents. The bacteria-derived immunotoxins were capable of destructing tumors with high specificity. These bacteria-based strategies for cancer treatment have shown potent anti-tumor effects both in vivo and in vitro, and some of them have proceeded to clinical trials. Pseudomonas aeruginosa, a Gram-negative bacterial pathogen, is one of the common bacteria used in development of bacteria-based cancer therapy, particularly known for the Pseudomonas exotoxin A-based immunotoxins, which have shown remarkable anti-tumor efficacy and specificity. This review concisely summarizes the current knowledge regarding the utilization of P. aeruginosa in cancer treatment, and discusses the challenges and future perspectives of the P. aeruginosa-based therapeutic strategies.

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P. aeruginosa Mediated Necroptosis in Mouse Tumor Cells Induces Long-Lasting Systemic Antitumor Immunity

Cited by 5 publications

References 45 publications

Necroptosis Contributes to Persistent Inflammation During Acute Leptospirosis

Necroptosis Contributes to Persistent Inflammation During Acute Leptospirosis

Microbes mediated immunogenic cell death in cancer immunotherapy

Pseudomonas aeruginosa in Cancer Therapy: Current Knowledge, Challenges and Future Perspectives

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