Mechanisms of Immune Evasion in Multiple Myeloma: Open Questions and Therapeutic Opportunities
Multiple myeloma (MM) is the second most common hematologic malignancy, characterized by a multi-step evolutionary path, which starts with an early asymptomatic stage, defined as monoclonal gammopathy of undetermined significance (MGUS) evolving to overt disease in 1% of cases per year, often throug...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-06-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/13/13/3213 |
| _version_ | 1797528544205602816 |
|---|---|
| author | Cirino Botta Francesco Mendicino Enrica Antonia Martino Ernesto Vigna Domenica Ronchetti Pierpaolo Correale Fortunato Morabito Antonino Neri Massimo Gentile |
| author_facet | Cirino Botta Francesco Mendicino Enrica Antonia Martino Ernesto Vigna Domenica Ronchetti Pierpaolo Correale Fortunato Morabito Antonino Neri Massimo Gentile |
| author_sort | Cirino Botta |
| collection | DOAJ |
| description | Multiple myeloma (MM) is the second most common hematologic malignancy, characterized by a multi-step evolutionary path, which starts with an early asymptomatic stage, defined as monoclonal gammopathy of undetermined significance (MGUS) evolving to overt disease in 1% of cases per year, often through an intermediate phase known as “smoldering” MM (sMM). Interestingly, while many genomic alterations (translocation, deletions, mutations) are usually found at early stages, they are not sufficient (alone) to determine disease evolution. The latter, indeed, relies on significant “epigenetic” alterations of different normal cell populations within the bone marrow (BM) niche, including the “evasion” from immune-system control. Additionally, MM cells could “educate” the BM immune microenvironment (BM-IM) towards a pro-inflammatory and immunosuppressive phenotype, which ultimately leads to disease evolution, drug resistance, and patients’ worse outcome. Indeed, it is not a case that the most important drugs for the treatment of MM include immunomodulatory agents (thalidomide, lenalidomide, and pomalidomide) and monoclonal antibodies (daratumumab, isatuximab, and elotuzumab). On these bases, in this review, we describe the most recent advances in the comprehension of the role of the different cells composing the BM-IM, and we discuss the potential molecular targets, which could represent new opportunities to improve current treatment strategies for MM patients. |
| first_indexed | 2024-03-10T10:00:54Z |
| format | Article |
| id | doaj.art-a490bc63a19a40eb87068706641e89cc |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T10:00:54Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-a490bc63a19a40eb87068706641e89cc2023-11-22T01:58:40ZengMDPI AGCancers2072-66942021-06-011313321310.3390/cancers13133213Mechanisms of Immune Evasion in Multiple Myeloma: Open Questions and Therapeutic OpportunitiesCirino Botta0Francesco Mendicino1Enrica Antonia Martino2Ernesto Vigna3Domenica Ronchetti4Pierpaolo Correale5Fortunato Morabito6Antonino Neri7Massimo Gentile8Hematology Unit, Annunziata Hospital of Cosenza, 87100 Cosenza, ItalyHematology Unit, Annunziata Hospital of Cosenza, 87100 Cosenza, ItalyHematology Unit, Annunziata Hospital of Cosenza, 87100 Cosenza, ItalyHematology Unit, Annunziata Hospital of Cosenza, 87100 Cosenza, ItalyDepartment of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, ItalyMedical Oncology Unit, Grand Metropolitan Hospital “Bianchi-Melacrino-Morelli”, 89124 Reggio Calabria, ItalyHematology and Bone Marrow Transplant Unit, Hemato-Oncology Department, Augusta Victoria Hospital, East Jerusalem 91191, IsraelDepartment of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, ItalyHematology Unit, Annunziata Hospital of Cosenza, 87100 Cosenza, ItalyMultiple myeloma (MM) is the second most common hematologic malignancy, characterized by a multi-step evolutionary path, which starts with an early asymptomatic stage, defined as monoclonal gammopathy of undetermined significance (MGUS) evolving to overt disease in 1% of cases per year, often through an intermediate phase known as “smoldering” MM (sMM). Interestingly, while many genomic alterations (translocation, deletions, mutations) are usually found at early stages, they are not sufficient (alone) to determine disease evolution. The latter, indeed, relies on significant “epigenetic” alterations of different normal cell populations within the bone marrow (BM) niche, including the “evasion” from immune-system control. Additionally, MM cells could “educate” the BM immune microenvironment (BM-IM) towards a pro-inflammatory and immunosuppressive phenotype, which ultimately leads to disease evolution, drug resistance, and patients’ worse outcome. Indeed, it is not a case that the most important drugs for the treatment of MM include immunomodulatory agents (thalidomide, lenalidomide, and pomalidomide) and monoclonal antibodies (daratumumab, isatuximab, and elotuzumab). On these bases, in this review, we describe the most recent advances in the comprehension of the role of the different cells composing the BM-IM, and we discuss the potential molecular targets, which could represent new opportunities to improve current treatment strategies for MM patients.https://www.mdpi.com/2072-6694/13/13/3213multiple myelomatumor immunologyanti-cancer immune responseimmunotherapymonoclonal antibodies |
| spellingShingle | Cirino Botta Francesco Mendicino Enrica Antonia Martino Ernesto Vigna Domenica Ronchetti Pierpaolo Correale Fortunato Morabito Antonino Neri Massimo Gentile Mechanisms of Immune Evasion in Multiple Myeloma: Open Questions and Therapeutic Opportunities Cancers multiple myeloma tumor immunology anti-cancer immune response immunotherapy monoclonal antibodies |
| title | Mechanisms of Immune Evasion in Multiple Myeloma: Open Questions and Therapeutic Opportunities |
| title_full | Mechanisms of Immune Evasion in Multiple Myeloma: Open Questions and Therapeutic Opportunities |
| title_fullStr | Mechanisms of Immune Evasion in Multiple Myeloma: Open Questions and Therapeutic Opportunities |
| title_full_unstemmed | Mechanisms of Immune Evasion in Multiple Myeloma: Open Questions and Therapeutic Opportunities |
| title_short | Mechanisms of Immune Evasion in Multiple Myeloma: Open Questions and Therapeutic Opportunities |
| title_sort | mechanisms of immune evasion in multiple myeloma open questions and therapeutic opportunities |
| topic | multiple myeloma tumor immunology anti-cancer immune response immunotherapy monoclonal antibodies |
| url | https://www.mdpi.com/2072-6694/13/13/3213 |
| work_keys_str_mv | AT cirinobotta mechanismsofimmuneevasioninmultiplemyelomaopenquestionsandtherapeuticopportunities AT francescomendicino mechanismsofimmuneevasioninmultiplemyelomaopenquestionsandtherapeuticopportunities AT enricaantoniamartino mechanismsofimmuneevasioninmultiplemyelomaopenquestionsandtherapeuticopportunities AT ernestovigna mechanismsofimmuneevasioninmultiplemyelomaopenquestionsandtherapeuticopportunities AT domenicaronchetti mechanismsofimmuneevasioninmultiplemyelomaopenquestionsandtherapeuticopportunities AT pierpaolocorreale mechanismsofimmuneevasioninmultiplemyelomaopenquestionsandtherapeuticopportunities AT fortunatomorabito mechanismsofimmuneevasioninmultiplemyelomaopenquestionsandtherapeuticopportunities AT antoninoneri mechanismsofimmuneevasioninmultiplemyelomaopenquestionsandtherapeuticopportunities AT massimogentile mechanismsofimmuneevasioninmultiplemyelomaopenquestionsandtherapeuticopportunities |