Functional characterization of NK cells in Mexican pediatric patients with acute lymphoblastic leukemia: Report from the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia

Valenzuela-Vázquez, Lucero; Núñez-Enríquez, Juan Carlos; Sánchez-Herrera, Jacqueline; Jiménez‐Hernández, Elva; Martín-Trejo, Jorge Alfonso; Espinoza-Hernández, Laura Eugenia; Medina-Sansón, Aurora; Flores-Villegas, Luz Victoria; Peñaloza-González, José Gabriel; Torres-Nava, José Refugio; Espinosa-Elizondo, Rosa Martha; Amador-Sánchez, Raquel; Santillán-Juárez, Jessica Denisse; Flores-Lujano, Janet; Pérez-Saldivar, María Luisa; García-López, Luis Ramiro; Castañeda-Echevarría, Alejandro; Rodriguez-Leyva, Francisco; Rosas-Vargas, Haydeé; Mata-Rocha, Minerva; Duarte-Rodríguez, David Aldebarán; Sepúlveda-Robles, Omar Alejandro; Mancilla-Herrera, Ismael; Mejı́a-Aranguré, Juan Manuel; Cruz-Muñoz, Mario Ernesto

doi:10.1371/journal.pone.0227314

Cited by 21 publications

(20 citation statements)

References 49 publications

(64 reference statements)

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“…The conditioning regimen and intensity, prior treatment regimens, prior recipient of cellular and immunotherapy, the interval between last treatment and CAR-T, as well as disease status at the time of CAR-T also contribute to the cumulative risk of infection after CAR-T. For instance, the duration and depth of neutropenia determine overall infection risk in patients receiving multi-agent cytotoxic chemotherapy, such as in acute leukemia and lymphoma. Further, NK and T-cell mediated cytotoxicity is impaired with patients with ALL and worse in patients with T-ALL compared to B-ALL 105 . Patients with chronic lymphocytic leukemia (CLL) and MM have an inherent predisposition to infections associated with hypogammaglobulinemia and compromised humoral immunity 106 , 107 , 108 .…”

Section: Infection Risks In Patients With Car-t Immunotherapymentioning

confidence: 98%

State of the CAR-T: Risk of Infections with Chimeric Antigen Receptor T-Cell Therapy and Determinants of SARS-CoV-2 Vaccine Responses

Meir

Abid

2021

Transplantation and Cellular Therapy

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Chimeric antigen receptor T-cell (CAR-T) therapy has shown unprecedented response rates in patients with relapsed/refractory (R/R) hematological malignancies. While CAR-T therapy renders hope to heavily pre-treated patients, the rapid commercialization and cumulative immunosuppression predispose patients to infections for a prolonged period. CAR-T poses distinctive short- and long-term toxicities and infection risks among patients who receive CAR-T after multiple prior treatments, often including hematopoietic cell transplantation. The acute toxicities include cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. The long-term B-cell depletion, hypogammaglobulinemia, and cytopenia further predispose patients to severe infections and abrogate the remission success achieved by the living drug. These on-target-off-tumor toxicities deplete B-cells across the entire lineage and further diminish immune responses to vaccines. Early observational data suggest that patients with hematologic malignancies may not mount an adequate humoral and cellular response to SARS-CoV-2 vaccines. In this review, we summarize the immune comprising factors indigenous to CAR-T recipients. We discuss the immunogenic potential of different SARS-CoV-2 vaccines based on the differences in the manufacturing platforms among CAR-T recipients. Given the lack of data related to the safety and efficacy of SARS-CoV-2 vaccines in this distinctively immunosuppressed cohort, we summarize the infection risks associated with FDA-approved CAR-T constructs and the potential determinants of vaccine responses. The review further highlights the potential need for booster vaccine dosing and the promise for heterologous prime-boosting in CAR-T recipients.

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Section: Infection Risks In Patients With Car-t Immunotherapymentioning

confidence: 98%

State of the CAR-T: Risk of Infections with Chimeric Antigen Receptor T-Cell Therapy and Determinants of SARS-CoV-2 Vaccine Responses

Meir

Abid

2021

Transplantation and Cellular Therapy

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“…Already in 1989, Gabrilovac et al observed impairment of NK cell function in ALL [122]. More recent studies confirmed alterations in the phenotype and cytotoxicity of NK cells derived from ALL patients [118,121]. As compared to healthy donors, NK cells from pediatric ALL patients had lower levels of NKp46 activating receptors and higher levels of inhibitory NKG2A receptors [118].…”

Section: Alterations In the Numbers And Activity Of Nk Cellsmentioning

confidence: 99%

“…Early studies showed that patients suffering from ALL have abnormal percentages and absolute numbers of NK cells [120]. Moreover, Valenzuela-Vazquez et al confirmed these observations in Hispanic ALL patients, especially in those diagnosed with T-ALL [121]. Already in 1989, Gabrilovac et al observed impairment of NK cell function in ALL [122].…”

Section: Alterations In the Numbers And Activity Of Nk Cellsmentioning

confidence: 99%

Mechanisms of Immune Evasion in Acute Lymphoblastic Leukemia

Pastorczak

Domka

Fidyt

et al. 2021

Cancers

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Acute lymphoblastic leukemia (ALL) results from a clonal expansion of abnormal lymphoid progenitors of B cell (BCP-ALL) or T cell (T-ALL) origin that invade bone marrow, peripheral blood, and extramedullary sites. Leukemic cells, apart from their oncogene-driven ability to proliferate and avoid differentiation, also change the phenotype and function of innate and adaptive immune cells, leading to escape from the immune surveillance. In this review, we provide an overview of the genetic heterogeneity and treatment of BCP- and T-ALL. We outline the interactions of leukemic cells in the bone marrow microenvironment, mainly with mesenchymal stem cells and immune cells. We describe the mechanisms by which ALL cells escape from immune recognition and elimination by the immune system. We focus on the alterations in ALL cells, such as overexpression of ligands for various inhibitory receptors, including anti-phagocytic receptors on macrophages, NK cell inhibitory receptors, as well as T cell immune checkpoints. In addition, we describe how developing leukemia shapes the bone marrow microenvironment and alters the function of immune cells. Finally, we emphasize that an immunosuppressive microenvironment can reduce the efficacy of chemo- and immunotherapy and provide examples of preclinical studies showing strategies for improving ALL treatment by targeting these immunosuppressive interactions.

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“…Indeed, NK cell abnormality or de ciency is a risk factor for CMV reactivation [46]. This condition could explain the occurrence of elevated CMV reactivation among patients with ALL described in this study and elsewhere, once NK cell abnormalities were already reported in these patients [47]. In this study, we did not assess the phenotype of NK cells in patients positive for CMV IgM to verify this correlation.…”

Section: Discussionmentioning

confidence: 78%

Prevalence and Recurrence Rates of Cytomegalovirus Infection among Patients with Hematological Diseases of the Brazilian Western Amazon

Silva

Pinheiro-Silva

Oliveira

et al. 2021

Preprint

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Purpose: Cytomegalovirus (CMV) is a worldwide distributed pathogen that may cause serious complications in patients with hematological diseases. This study aimed to serologically characterize the CMV infection in patients suffering from hematological diseases in Amazonas, Brazil. Methods: Serum samples from 323 patients were tested for the presence of anti-CMV IgM or IgG antibodies by an enzyme-linked immunosorbent assay. Positive samples for IgM were submitted to the IgG avidity test to differentiate primary infection from recurrent infection. An epidemiological questionnaire was administered to collect sociodemographic information of the study population. Results: The overall prevalence of CMV infection verified in this study was 91.3%. The highest rates were found in patients suffering from platelet disorders (94.5%), anemia (93.3%), or leukemia (91%). The study population was predominantly composed of individuals with low socioeconomic status. Blood transfusions were more often in patients with anemia or leukemia, but it was not correlated with the positivity for CMV infection. Measurement of IgG avidity in patients positive for anti-CMV IgM demonstrated a recurrent infection rate of 5.2% (17/323). Over 80% of recurrent infection occurred in patients with acute lymphocytic leukemia (ALL) or anemia. Conclusions: Our findings indicated that CMV infection is highly prevalent in patients with hematological diseases from the Brazilian western Amazon. The prevalence observed progressively rose with increasing age, whereas anemia or ALL disease figured as risk factors for the recurrence of CMV infection.

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Functional characterization of NK cells in Mexican pediatric patients with acute lymphoblastic leukemia: Report from the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia

Abstract: Acute lymphoblastic leukemia (ALL) is the most common cancer in children around the globe. Mexico City has one of the highest incidence rates of childhood leukemia worldwide with 49.5 cases per million children under the age of 15 which is similar to that reported for

Cited by 21 publications

References 49 publications

State of the CAR-T: Risk of Infections with Chimeric Antigen Receptor T-Cell Therapy and Determinants of SARS-CoV-2 Vaccine Responses

State of the CAR-T: Risk of Infections with Chimeric Antigen Receptor T-Cell Therapy and Determinants of SARS-CoV-2 Vaccine Responses

Mechanisms of Immune Evasion in Acute Lymphoblastic Leukemia

Prevalence and Recurrence Rates of Cytomegalovirus Infection among Patients with Hematological Diseases of the Brazilian Western Amazon

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