The potentials of immune checkpoints for the treatment of blood malignancies

Alizadeh, Mohammad; Safarzadeh, Ali; Hoseini, Seyed Ali; Piryaei, Reza; Mansoori, Behzad; Hajiasgharzadeh, Khalil; Baghbanzadeh, Amir; Baradaran, Behzad

doi:10.1016/j.critrevonc.2020.103031

Cited by 5 publications

(6 citation statements)

References 173 publications

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“…In several different cases, the immunologic disorders have been described before the hematological disorders diagnosis, whilst in other cases the immune alterations have been reported after hematological neoplasm onset or during treatment. In this line, immunosuppressive therapies such as immune checkpoint inhibitors, INF-alpha, corticosteroids, monoclonal antibodies and cytotoxic drugs, may induce immunological perturbations and/or rheumatic manifestations during the management of hematological patients [ 31 – 33 ].…”

Section: Discussionmentioning

confidence: 99%

Correlation analysis between auto-immunological and mutational profiles in myelodysplastic syndromes

et al. 2023

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Objective and design Systemic-Inflammatory-Autoimmune-Diseases (SIAD) is increasingly considered in Myelodysplastic-Syndromes (MDS). In this line, we evaluated the MDS auto-immunological profile, correlating it to the mutational landscape, trying to identify a molecular-genetic trigger agent related to SIAD. Methods and materials Eighty-one MDS were enrolled and t-NGS was performed. Anti-Nuclear-Antibodies (ANA) were tested, and ANA-antigenic-specificity was characterized by ANA-profile, ENA-screen, anti-dsDNA. Non-Hematological-Patients (NHP) and Healthy-Donors (HD) were used as controls. Results At clinically relevant cut-off (≥ 1:160), ANA was significantly more frequent in MDS, while ANA-antigenic-specificity showed a low association rate. ANA ≥ 1:160-positive MDS showed a mutational landscape similar to ANA-negative/ANA < 1:160 MDS. No significant correlations between mutational and immunological profiles were found and UBA1 mutations, related to VEXAS, were absent. Conclusions Although ANA-positivity was found to be increased in MDS, the low ANA-antigenic-specificity suggests that autoantibodies didn’t recognize autoimmune-pathognomonic antigens. The lack of relationship between genetic profile and ANA-positivity, suggests that MDS genetic variants may not be the direct cause of SIAD.

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Section: Discussionmentioning

confidence: 99%

Correlation analysis between auto-immunological and mutational profiles in myelodysplastic syndromes

et al. 2023

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“…Immune checkpoint blockers act by activating co-stimulatory signals and blocking inhibitory signals. The discovery of novel immune checkpoint molecules as potential cancer therapeutics resulted in a substantial increase in studies involving novel therapeutic agents [ 169 ]. Here, we will highlight the functional role of co-stimulatory and inhibitory ICs in AML by focusing on signaling mechanisms that cause angiogenesis, metastasis, and cell proliferation in this malignancy.…”

Section: Immune Checkpoints’ Roles In Aml Angiogenesis Metastasis And...mentioning

confidence: 99%

“…Cancerous cells escape immunity by disrupting immune checkpoints intelligently. novel therapeutic agents [169]. Here, we will highlight the functional role of co-stimulatory and inhibitory ICs in AML by focusing on signaling mechanisms that cause angiogenesis, metastasis, and cell proliferation in this malignancy.…”

Section: Immune Checkpoints' Roles In Aml Angiogenesis Metastasis And...mentioning

confidence: 99%

The role of bone marrow microenvironment (BMM) cells in acute myeloid leukemia (AML) progression: immune checkpoints, metabolic checkpoints, and signaling pathways

Bakhtiyari,

Liaghat,

Aziziyan

et al. 2023

Cell Commun Signal

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Acute myeloid leukemia (AML) comprises a multifarious and heterogeneous array of illnesses characterized by the anomalous proliferation of myeloid cells in the bone marrow microenvironment (BMM). The BMM plays a pivotal role in promoting AML progression, angiogenesis, and metastasis. The immune checkpoints (ICs) and metabolic processes are the key players in this process. In this review, we delineate the metabolic and immune checkpoint characteristics of the AML BMM, with a focus on the roles of BMM cells e.g. tumor-associated macrophages, natural killer cells, dendritic cells, metabolic profiles and related signaling pathways. We also discuss the signaling pathways stimulated in AML cells by BMM factors that lead to AML progression. We then delve into the roles of immune checkpoints in AML angiogenesis, metastasis, and cell proliferation, including co-stimulatory and inhibitory ICs. Lastly, we discuss the potential therapeutic approaches and future directions for AML treatment, emphasizing the potential of targeting metabolic and immune checkpoints in AML BMM as prognostic and therapeutic targets. In conclusion, the modulation of these processes through the use of directed drugs opens up new promising avenues in combating AML. Thereby, a comprehensive elucidation of the significance of these AML BMM cells' metabolic and immune checkpoints and signaling pathways on leukemic cells can be undertaken in the future investigations. Additionally, these checkpoints and cells should be considered plausible multi-targeted therapies for AML in combination with other conventional treatments in AML.

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“…Well known toxicities of CAR T-cells also derive from a complex immune dysregulation and include the cytokine release syndrome, the immune effector cell-associated neurotoxicity syndrome, and the hemophagocytic lymphohistiocytosis; later toxicities comprise prolonged cytopenias and hypogammaglobulinemia (62). Finally, the difficulty of a balanced immune stimulation is also highlighted by the autoimmune complications following therapy with check point inhibitors in solid and hematologic tumors (63,64).…”

Section: Autoimmune Complications Following Therapy Of Myeloid Neoplasmsmentioning

confidence: 99%

Immune Phenomena in Myeloid Neoplasms: An “Egg or Chicken” Question

Barcellini

Fattizzo

2021

Front. Immunol.

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Immune phenomena are increasingly reported in myeloid neoplasms, and include autoimmune cytopenias/diseases and immunodeficiency, either preceding or complicating acute myeloid leukemia, myelodysplastic syndromes (MDS), chronic myeloproliferative neoplasms, and bone marrow failure (BMF) syndromes. Autoimmunity and immunodeficiency are the two faces of a dysregulated immune tolerance and surveillance and may result, along with contributing environmental and genetic factors, in an increased incidence of both tumors and infections. The latter may fuel both autoimmunity and immune activation, triggering a vicious circle among infections, tumors and autoimmune phenomena. Additionally, alterations of the microbiota and of mesenchymal stem cells (MSCs) pinpoint to the importance of a permissive or hostile microenvironment for tumor growth. Finally, several therapies of myeloid neoplasms are aimed at increasing host immunity against the tumor, but at the price of increased autoimmune phenomena. In this review we will examine the epidemiological association of myeloid neoplasms with autoimmune diseases and immunodeficiencies, and the pivotal role of autoimmunity in the pathogenesis of MDS and BMF syndromes, including the paroxysmal nocturnal hemoglobinuria conundrum. Furthermore, we will briefly examine autoimmune complications following therapy of myeloid neoplasms, as well as the role of MSCs and microbiota in these settings.

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The potentials of immune checkpoints for the treatment of blood malignancies

Cited by 5 publications

References 173 publications

Correlation analysis between auto-immunological and mutational profiles in myelodysplastic syndromes

Correlation analysis between auto-immunological and mutational profiles in myelodysplastic syndromes

The role of bone marrow microenvironment (BMM) cells in acute myeloid leukemia (AML) progression: immune checkpoints, metabolic checkpoints, and signaling pathways

Immune Phenomena in Myeloid Neoplasms: An “Egg or Chicken” Question

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