1-MT inhibits the invasion of CBP-resistant ovarian cancer cells via down-regulating IDO expression and re-activating immune cells function

Ma, Han; Qin, Qian; Mi, Jiaqing; Feng, Qinmei

doi:10.1186/s40360-020-00439-w

Cited by 3 publications

(3 citation statements)

References 24 publications

(31 reference statements)

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“…Preclinical research showed that IDO1 inhibition by 1-MT also counteracts the invasion of carboplatin-resistant ovarian cancer cells via the down-regulation of IDO expression and re-activation of immune cell function. Thus, inhibition of the KP activity seems to be a potentially effective solution in the case of carboplatin-resistant cancers ( Table 1 ) [ 46 , 129 ].…”

Section: Modulation Of Kynurenine Pathway Activity In the Management Of Neoplastic Diseasesmentioning

confidence: 99%

“…[ 43 , 44 , 45 , 46 , 47 , 181 ]. Additionally, recent preclinical evidence indicates that the IDO1 inhibitors synergize the effects of tumor immuno- and chemotherapies and help to solve the problem of tumor resistance against them [ 83 , 93 , 105 , 106 , 107 , 108 , 112 , 113 , 119 , 120 , 129 , 132 , 133 , 136 , 137 , 143 , 146 , 151 , 154 , 155 , 156 , 157 , 171 ]. In turn, the discoveries concerning the role of IDO1 in tumor angiogenesis suggest that inhibiting its activity may effectively suppress this process, providing a potentially effective solution in the prevention of tumor development and metastasis.…”

Section: Summary and Future Directionsmentioning

confidence: 99%

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Kynurenines as a Novel Target for the Treatment of Malignancies

2021

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Malignancies are unquestionably a significant public health problem. Their effective treatment is still a big challenge for modern medicine. Tumors have developed a wide range of mechanisms to evade an immune and therapeutic response. As a result, there is an unmet clinical need for research on solutions aimed at overcoming this problem. An accumulation of tryptophan metabolites belonging to the kynurenine pathway can enhance neoplastic progression because it causes the suppression of immune system response against cancer cells. They are also involved in the development of the mechanisms responsible for the resistance to antitumor therapy. Kynurenine belongs to the most potent immunosuppressive metabolites of this pathway and has a significant impact on the development of malignancies. This fact prompted researchers to assess whether targeting the enzymes responsible for its synthesis could be an effective therapeutic strategy for various cancers. To date, numerous studies, both preclinical and clinical, have been conducted on this topic, especially regarding the inhibition of indoleamine 2,3-dioxygenase activity and their results can be considered noteworthy. This review gathers and systematizes the knowledge about the role of the kynurenine pathway in neoplastic progression and the findings regarding the usefulness of modulating its activity in anticancer therapy.

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Section: Modulation Of Kynurenine Pathway Activity In the Management Of Neoplastic Diseasesmentioning

confidence: 99%

Section: Summary and Future Directionsmentioning

confidence: 99%

Kynurenines as a Novel Target for the Treatment of Malignancies

2021

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“…CD4 + T cells are the most sensitive to this change [ 14 , 15 ]. Many studies have found that 1-methyltroptophan (1-MT) has a good inhibitory effect on IDO [ 16 , 17 ]. Studies have shown that the excretory–secretory (ES) antigen of Trichinella spiralis (T. spiralis ) can increase the expression of IDO and facilitate immune tolerance [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Alleviation of Rheumatoid Arthritis by Inducing IDO Expression with Trichinella spiralis Recombinant Protein 43

Ma,

Liu,

et al. 2024

Journal of Immunology Research

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Rheumatoid arthritis (RA) represents the autoimmune disorder that shows aggressive arthritis as the main symptom. It is difficult to treat and can lead to joint deformation and function loss. At present, Trichinella spiralis (T. spiralis) antigen has attracted much attention because it plays a role in host immune regulatory mechanisms. Therefore, we selected T. spiralis recombinant protein 43 (Tsp43) to treat the bovine collagen type II (BCII)-induced mice RA model and explored its therapeutic mechanisms. This work first verified that Tsp43 could promote the expression of indoleamine 2, 3-dioxygenase (IDO) in dendritic cells (DCs) in vitro. Then, we randomized BALB/c mice (8 weeks old) into six groups, including control, phosphate buffer saline (PBS), BCII, BCII + heat inactivated Tsp43 (HiTsp43), BCII + Tsp43, and BCII + Tsp43 + 1-methyl-troptophan (1-MT) groups. To determine the therapeutic effect of Tsp43 on the BCII-induced mice RA model, relevant cytokines in each group and pathological changes in ankle joints were detected. To explore the mechanisms of Tsp43 on the BCII-induced mice RA model, we checked the expression of IDO in each group, CD4+T cell proliferation, and apoptosis. Collectively, Tsp43 decreased tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) expression in BCII-induced mice RA model and recovered the ankle injury to a certain extent. Tsp43 promoted high expression of IDO, caused expression of related apoptotic proteins in CD4+T cells, and caused apoptosis in CD4+T cells. In addition, Tsp43 reduced the proliferation of CD4+T cells. However, these effects can be inhibited by 1-MT (IDO inhibitor). These results suggested that Tsp43 played an important role in the treatment of arthritis by inhibiting the proliferation of CD4+T cells and inducing CD4+T cells apoptosis through the high expression of IDO. The purpose of this experiment was to provide a new idea for the treatment of RA and lay a foundation for the development of parasite-derived drugs for the treatment of RA.

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Targeting tumor-associated macrophages for successful immunotherapy of ovarian carcinoma

Truxová

Cibula

Špíšek

et al. 2023

J Immunother Cancer

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Epithelial ovarian cancer (EOC) is among the top five causes of cancer-related death in women, largely reflecting early, prediagnosis dissemination of malignant cells to the peritoneum. Despite improvements in medical therapies, particularly with the implementation of novel drugs targeting homologous recombination deficiency, the survival rates of patients with EOC remain low. Unlike other neoplasms, EOC remains relatively insensitive to immune checkpoint inhibitors, which is correlated with a tumor microenvironment (TME) characterized by poor infiltration by immune cells and active immunosuppression dominated by immune components with tumor-promoting properties, especially tumor-associated macrophages (TAMs). In recent years, TAMs have attracted interest as potential therapeutic targets by seeking to reverse the immunosuppression in the TME and enhance the clinical efficacy of immunotherapy. Here, we review the key biological features of TAMs that affect tumor progression and their relevance as potential targets for treating EOC. We especially focus on the therapies that might modulate the recruitment, polarization, survival, and functional properties of TAMs in the TME of EOC that can be harnessed to develop superior combinatorial regimens with immunotherapy for the clinical care of patients with EOC.

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1-MT inhibits the invasion of CBP-resistant ovarian cancer cells via down-regulating IDO expression and re-activating immune cells function

Cited by 3 publications

References 24 publications

Kynurenines as a Novel Target for the Treatment of Malignancies

Kynurenines as a Novel Target for the Treatment of Malignancies

Alleviation of Rheumatoid Arthritis by Inducing IDO Expression with Trichinella spiralis Recombinant Protein 43

Targeting tumor-associated macrophages for successful immunotherapy of ovarian carcinoma

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