Antitumor Effect of IL-2 and TRAIL Proteins Expressed by Recombinant Salmonella in Murine Bladder Cancer Cells

Fragelli, Bruna Dias de Lima; Camillo, Luciana; Rodolpho, Joice Margareth de Almeida; Godoy, Krissia Franco de; Castro, Cynthia Aparecida de; Brassolatti, Patrícia; Silva, A. J. da; Borra, Ricardo Carneiro; Aníbal, Fernanda de Freitas

doi:10.33594/000000398

Cited by 5 publications

(3 citation statements)

References 56 publications

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“…Subsequently, three major signaling pathways, including PI3K-AKT, JAK-STAT, and MAPK/ERK are activated [ 149 ] to mediate cell growth, survival, and differentiation, and cytokine production (IL-4, IL-6, IL-12) [ 150 , 151 ]. Thus, in breast cancer [ 389 ], IL-2 plays an anti-tumor effect [ 390 ] due to increased recruitment of IL-2-releasing NK cells and the induction of anti-apoptotic function in CD8 + T cells [ 391 ], the main effector of the antitumor response [ 392 ]. IL-2 can promote activation and proliferation of CD8 + T cells in early tumor stage but can deplete CD8 + T cells in late tumor stage [ 393 ] ( Figure 1 ).…”

Section: Interleukin-2 (Il-2)mentioning

confidence: 99%

Crosstalk of Inflammatory Cytokines within the Breast Tumor Microenvironment

Habanjar

Bingula

Decombat

et al. 2023

IJMS

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Several immune and immunocompetent cells, including dendritic cells, macrophages, adipocytes, natural killer cells, T cells, and B cells, are significantly correlated with the complex discipline of oncology. Cytotoxic innate and adaptive immune cells can block tumor proliferation, and others can prevent the immune system from rejecting malignant cells and provide a favorable environment for tumor progression. These cells communicate with the microenvironment through cytokines, a chemical messenger, in an endocrine, paracrine, or autocrine manner. These cytokines play an important role in health and disease, particularly in host immune responses to infection and inflammation. They include chemokines, interleukins (ILs), adipokines, interferons, colony-stimulating factors (CSFs), and tumor necrosis factor (TNF), which are produced by a wide range of cells, including immune cells, such as macrophages, B-cells, T-cells, and mast cells, as well as endothelial cells, fibroblasts, a variety of stromal cells, and some cancer cells. Cytokines play a crucial role in cancer and cancer-related inflammation, with direct and indirect effects on tumor antagonistic or tumor promoting functions. They have been extensively researched as immunostimulatory mediators to promote the generation, migration and recruitment of immune cells that contribute to an effective antitumor immune response or pro-tumor microenvironment. Thus, in many cancers such as breast cancer, cytokines including leptin, IL-1B, IL-6, IL-8, IL-23, IL-17, and IL-10 stimulate while others including IL-2, IL-12, and IFN-γ, inhibit cancer proliferation and/or invasion and enhance the body’s anti-tumor defense. Indeed, the multifactorial functions of cytokines in tumorigenesis will advance our understanding of cytokine crosstalk pathways in the tumor microenvironment, such as JAK/STAT, PI3K, AKT, Rac, MAPK, NF-κB, JunB, cFos, and mTOR, which are involved in angiogenesis, cancer proliferation and metastasis. Accordingly, targeting and blocking tumor-promoting cytokines or activating and amplifying tumor-inhibiting cytokines are considered cancer-directed therapies. Here, we focus on the role of the inflammatory cytokine system in pro- and anti-tumor immune responses, discuss cytokine pathways involved in immune responses to cancer and some anti-cancer therapeutic applications.

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Section: Interleukin-2 (Il-2)mentioning

confidence: 99%

Crosstalk of Inflammatory Cytokines within the Breast Tumor Microenvironment

Habanjar

Bingula

Decombat

et al. 2023

IJMS

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“…The researchers inserted IL-2 or/and TRAIL genes into the genome of attenuated Salmonella strain SL3261 and examined the effect of this Salmonella strain on BC in mice. The recombinant SL3261 strain caused cell membrane damage, increased NO production, and promoted apoptosis in mouse BC M49 cells [ 94 ]. Butler et al also showed that uropathogenic E. coli degraded c-MYC protein and attenuated MYC expression in tumor cells.…”

Section: Microbiota and Bladder Tumorigenesismentioning

confidence: 99%

Bladder cancer-associated microbiota: Recent advances and future perspectives

Zhang

Yang

Mao

et al. 2023

Heliyon

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“…The engineering plasticity of Salmonella enhances its efficacy in cancer therapy through improving safety, specificity, and delivery of anti-tumor therapeutic agents. It has been exploited for the delivery of cytotoxic agents such as cytolysin A, PE38, and diphtheria toxin, apoptosis-inducing proteins such as Fas ligand and TNF-related, apoptosis-inducing ligand (TRAIL), as well as apoptin and immunomodulatory cytokines, including IL-2, IL-12, IL-18, and IFN-γ [ 34 , 42 , 43 , 44 , 45 , 46 ]. Engineering plasticity enables the application of Salmonella in the expression of anti-cancer agents, “prodrugs,” or tumor-specific antigens at tumor sites.…”

Section: Why Is Salmonella the Best Option?mentioning

confidence: 99%

Salmonella as a Promising Curative Tool against Cancer

2022

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Bacteria-mediated cancer therapy has become a topic of interest under the broad umbrella of oncotherapy. Among many bacterial species, Salmonella remains at the forefront due to its ability to localize and proliferate inside tumor microenvironments and often suppress tumor growth. Salmonella Typhimurium is one of the most promising mediators, with engineering plasticity and cancer specificity. It can be used to deliver toxins that induce cell death in cancer cells specifically, and also as a cancer-specific instrument for immunotherapy by delivering tumor antigens and exposing the tumor environment to the host immune system. Salmonella can be used to deliver prodrug converting enzymes unambiguously against cancer. Though positive responses in Salmonella-mediated cancer treatments are still at a preliminary level, they have paved the way for developing combinatorial therapy with conventional chemotherapy, radiotherapy, and surgery, and can be used synergistically to combat multi-drug resistant and higher-stage cancers. With this background, Salmonella-mediated cancer therapy was approved for clinical trials by U.S. Food and Drug Administration, but the results were not satisfactory and more pre-clinical investigation is needed. This review summarizes the recent advancements in Salmonella-mediated oncotherapy in the fight against cancer. The present article emphasizes the demand for Salmonella mutants with high stringency toward cancer and with amenable elements of safety by virulence deletions.

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Antitumor Effect of IL-2 and TRAIL Proteins Expressed by Recombinant Salmonella in Murine Bladder Cancer Cells

Cited by 5 publications

References 56 publications

Crosstalk of Inflammatory Cytokines within the Breast Tumor Microenvironment

Crosstalk of Inflammatory Cytokines within the Breast Tumor Microenvironment

Bladder cancer-associated microbiota: Recent advances and future perspectives

Salmonella as a Promising Curative Tool against Cancer

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