Targeting immunometabolism mediated by the IDO1 Pathway: A new mechanism of immune resistance in endometrial cancer
Immunotherapy is acquiring a primary role in treating endometrial cancer (EC) with a relevant benefit for many patients. Regardless, patients progressing during immunotherapy or those who are resistant represent an unmet need. The mechanisms of immune resistance and escape need to be better investig...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.953115/full |
| _version_ | 1828117751120527360 |
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| author | Anna Passarelli Carmela Pisano Sabrina Chiara Cecere Marilena Di Napoli Sabrina Rossetti Rosa Tambaro Jole Ventriglia Federica Gherardi Eva Iannacone Sergio Setola Venanzio Francesco Fiore Michele Bartoletti Giosuè Scognamiglio Daniela Califano Sandro Pignata |
| author_facet | Anna Passarelli Carmela Pisano Sabrina Chiara Cecere Marilena Di Napoli Sabrina Rossetti Rosa Tambaro Jole Ventriglia Federica Gherardi Eva Iannacone Sergio Setola Venanzio Francesco Fiore Michele Bartoletti Giosuè Scognamiglio Daniela Califano Sandro Pignata |
| author_sort | Anna Passarelli |
| collection | DOAJ |
| description | Immunotherapy is acquiring a primary role in treating endometrial cancer (EC) with a relevant benefit for many patients. Regardless, patients progressing during immunotherapy or those who are resistant represent an unmet need. The mechanisms of immune resistance and escape need to be better investigated. Here, we review the major mechanisms of immune escape activated by the indolamine 2,3-dioxygenase 1 (IDO1) pathway in EC and focus on potential therapeutic strategies based on IDO1 signaling pathway control. IDO1 catalyzes the first rate-limiting step of the so-called “kynurenine (Kyn) pathway”, which converts the essential amino acid l-tryptophan into the immunosuppressive metabolite l-kynurenine. Functionally, IDO1 has played a pivotal role in cancer immune escape by catalyzing the initial step of the Kyn pathway. The overexpression of IDO1 is also associated with poor prognosis in EC. These findings can lead to advantages in immunotherapy-based approaches as a rationale for overcoming the immune escape. Indeed, besides immune checkpoints, other mechanisms, including the IDO enzymes, contribute to the EC progression due to the immunosuppression induced by the tumor milieu. On the other hand, the IDO1 enzyme has recently emerged as both a promising therapeutic target and an unfavorable prognostic biomarker. This evidence provides the basis for translational strategies of immune combination, whereas IDO1 expression would serve as a potential prognostic biomarker in metastatic EC. |
| first_indexed | 2024-04-11T13:20:29Z |
| format | Article |
| id | doaj.art-a566ec8355c14cb985e3d260165dc78e |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T13:20:29Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-a566ec8355c14cb985e3d260165dc78e2022-12-22T04:22:14ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-09-011310.3389/fimmu.2022.953115953115Targeting immunometabolism mediated by the IDO1 Pathway: A new mechanism of immune resistance in endometrial cancerAnna Passarelli0Carmela Pisano1Sabrina Chiara Cecere2Marilena Di Napoli3Sabrina Rossetti4Rosa Tambaro5Jole Ventriglia6Federica Gherardi7Eva Iannacone8Sergio Setola Venanzio9Francesco Fiore10Michele Bartoletti11Giosuè Scognamiglio12Daniela Califano13Sandro Pignata14Department of Urology and Gynecology, Istituto Nazionale Tumori Istituto di Ricovero e Cura a Carattere Scientifico Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Fondazione G. Pascale, Naples, ItalyDepartment of Urology and Gynecology, Istituto Nazionale Tumori Istituto di Ricovero e Cura a Carattere Scientifico Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Fondazione G. Pascale, Naples, ItalyDepartment of Urology and Gynecology, Istituto Nazionale Tumori Istituto di Ricovero e Cura a Carattere Scientifico Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Fondazione G. Pascale, Naples, ItalyDepartment of Urology and Gynecology, Istituto Nazionale Tumori Istituto di Ricovero e Cura a Carattere Scientifico Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Fondazione G. Pascale, Naples, ItalyDepartment of Urology and Gynecology, Istituto Nazionale Tumori Istituto di Ricovero e Cura a Carattere Scientifico Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Fondazione G. Pascale, Naples, ItalyDepartment of Urology and Gynecology, Istituto Nazionale Tumori Istituto di Ricovero e Cura a Carattere Scientifico Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Fondazione G. Pascale, Naples, ItalyDepartment of Urology and Gynecology, Istituto Nazionale Tumori Istituto di Ricovero e Cura a Carattere Scientifico Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Fondazione G. Pascale, Naples, ItalyRadiation Oncology Unit, Istituto Nazionale Tumori Istituto di Ricovero e Cura a Carattere Scientifico Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Fondazione G. Pascale, Naples, ItalyRadiation Oncology Unit, Istituto Nazionale Tumori Istituto di Ricovero e Cura a Carattere Scientifico Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Fondazione G. Pascale, Naples, ItalyRadiology Unit, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples, ItalyInterventional Radiology Unit, Istituto Nazionale Tumori Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Fondazione G. Pascale, Naples, ItalyMedical Oncology and Cancer Prevention Unit, Department of Medical Oncology, Oncology Referral Center, Aviano, ItalySurgical Pathology Unit, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples, ItalyFunctional Genomic Unit, Istituto Nazionale Tumori Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Fondazione G. Pascale, Naples, ItalyDepartment of Urology and Gynecology, Istituto Nazionale Tumori Istituto di Ricovero e Cura a Carattere Scientifico Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Fondazione G. Pascale, Naples, ItalyImmunotherapy is acquiring a primary role in treating endometrial cancer (EC) with a relevant benefit for many patients. Regardless, patients progressing during immunotherapy or those who are resistant represent an unmet need. The mechanisms of immune resistance and escape need to be better investigated. Here, we review the major mechanisms of immune escape activated by the indolamine 2,3-dioxygenase 1 (IDO1) pathway in EC and focus on potential therapeutic strategies based on IDO1 signaling pathway control. IDO1 catalyzes the first rate-limiting step of the so-called “kynurenine (Kyn) pathway”, which converts the essential amino acid l-tryptophan into the immunosuppressive metabolite l-kynurenine. Functionally, IDO1 has played a pivotal role in cancer immune escape by catalyzing the initial step of the Kyn pathway. The overexpression of IDO1 is also associated with poor prognosis in EC. These findings can lead to advantages in immunotherapy-based approaches as a rationale for overcoming the immune escape. Indeed, besides immune checkpoints, other mechanisms, including the IDO enzymes, contribute to the EC progression due to the immunosuppression induced by the tumor milieu. On the other hand, the IDO1 enzyme has recently emerged as both a promising therapeutic target and an unfavorable prognostic biomarker. This evidence provides the basis for translational strategies of immune combination, whereas IDO1 expression would serve as a potential prognostic biomarker in metastatic EC.https://www.frontiersin.org/articles/10.3389/fimmu.2022.953115/fullendometrial cancerindolamine 23-dioxygenase (IDO)tryptophankynurenineimmune metabolism |
| spellingShingle | Anna Passarelli Carmela Pisano Sabrina Chiara Cecere Marilena Di Napoli Sabrina Rossetti Rosa Tambaro Jole Ventriglia Federica Gherardi Eva Iannacone Sergio Setola Venanzio Francesco Fiore Michele Bartoletti Giosuè Scognamiglio Daniela Califano Sandro Pignata Targeting immunometabolism mediated by the IDO1 Pathway: A new mechanism of immune resistance in endometrial cancer Frontiers in Immunology endometrial cancer indolamine 2 3-dioxygenase (IDO) tryptophan kynurenine immune metabolism |
| title | Targeting immunometabolism mediated by the IDO1 Pathway: A new mechanism of immune resistance in endometrial cancer |
| title_full | Targeting immunometabolism mediated by the IDO1 Pathway: A new mechanism of immune resistance in endometrial cancer |
| title_fullStr | Targeting immunometabolism mediated by the IDO1 Pathway: A new mechanism of immune resistance in endometrial cancer |
| title_full_unstemmed | Targeting immunometabolism mediated by the IDO1 Pathway: A new mechanism of immune resistance in endometrial cancer |
| title_short | Targeting immunometabolism mediated by the IDO1 Pathway: A new mechanism of immune resistance in endometrial cancer |
| title_sort | targeting immunometabolism mediated by the ido1 pathway a new mechanism of immune resistance in endometrial cancer |
| topic | endometrial cancer indolamine 2 3-dioxygenase (IDO) tryptophan kynurenine immune metabolism |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.953115/full |
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