Ig-Like Transcript 2 (ILT2) Blockade and Lenalidomide Restore NK Cell Function in Chronic Lymphocytic Leukemia

One of the cardinal features of chronic lymphocytic leukemia (CLL) is its association with a profound immunosuppression. NK cell function is markedly impaired in CLL patients, who show a significant dysregulation of the expression of activating and inhibitory receptors. Here, we analyzed the role of the novel inhibitory receptor Ig-like transcript 2 (ILT2, also termed LIR-1, LILRB1) in the regulation of NK cells in CLL. Our results show that ILT2 expression was significantly decreased on leukemic cells and increased on NK cells of CLL patients, particularly in those with advanced disease and with bad prognostic features, such as those carrying chromosome del(11q). The immunomodulatory drug lenalidomide may regulate the expression of ILT2 and its ligands in CLL since it significantly increased the expression of ILT2 and partially reestablished the expression of its ligands on leukemic cells. Furthermore, lenalidomide significantly increased the activation and proliferation of NK cells, which was strongly enhanced by ILT2 blockade. Combining ILT2 blockade and lenalidomide activated NK cell cytotoxicity resulting in increased elimination of leukemic cells from CLL patients. Overall, we describe herein the role of an inhibitory receptor involved in the suppression of NK cell activity in CLL, which is restored by ILT2 blockade in combination with lenalidomide, suggesting that it may be an interesting therapeutic strategy to be explored in this disease

Educación para el siglo XXI: Derechos humanos, ciudadanía y diversidad sexual

172 p. Libro ElectrónicoEste libro recoge el resultado de la sistematización del programa “Maestros y maestras que inspiran” de la línea de Derechos humanos, ciudadanía y diversidad sexual. Estos documentos contienen los relatos de los docentes participantes, como resultado del trabajo dentro y fuera de las aulas en diferentes colegios del Distrito Capital. Los docentes narran sus experiencias desde los diversos contextos, así como las diferentes metodologías utilizadas todas con el fin de forta-lecer la ciudadanía, no solo de sus estudiantes, sino de ellos mismos, de padres y madres de familia y la comunidad en general. Finalmente nos cuentan, cuáles fueron los principales logros y las recomendacio-nes para otros docentes que quieran seguir sus pasos

Associated factors for mortality in a COVID-19 colombian cohort : is the third wave relevant when Mu variant was predominant epidemiologically?

Q1Q1Pacientes con COVID-19Objectives: To evaluate the association between Colombia's third wave when the Mu variant was predominant epidemiologically (until 75%) in Colombia and COVID-19 all-cause in-hospital mortality. Methods: In this retrospective cohort, we included hospitalized patients ≥18 years with SARS-CoV-2 infection between March 2020 to September 2021 in ten hospitals from three cities in Colombia. Description analysis, survival, and multivariate Cox regression analyses were performed to evaluate the association between the third epidemic wave and in-hospital mortality. Results: A total of 25,371 patients were included. The age-stratified time-to-mortality curves showed differences according to epidemic waves in patients ≥75 years (log-rank test p = 0.012). In the multivariate Cox analysis, the third wave was not associated with increased mortality relative to the first wave (aHR 0.95; 95%CI 0.84–1.08), but there was an interaction between age ≥75 years and the third wave finding a lower HR for mortality (aHR 0.56, 95%CI 0.36–0.86). Conclusions: We did not find an increase in in-hospital mortality during the third epidemic wave in which the Mu variant was predominant in Colombia. The reduced hazard in mortality in patients ≥75 years hospitalized in the third wave could be explained by the high coverage of SARS-CoV-2 vaccination in this population and patients with underlying conditions.https://orcid.org/0000-0003-1833-1599https://orcid.org/0000-0001-5363-5729https://orcid.org/0000-0001-6964-2229https://orcid.org/0000-0003-3975-2835https://orcid.org/0000-0001-9441-4375Revista Internacional - IndexadaA1N

Symptom cluster analysis of long COVID-19 in patients discharged from the Temporary COVID-19 Hospital in Mexico City.

INTRODUCTION: Several reports have emerged describing the long-term consequences of COVID-19 and its effects on multiple systems. METHODS: As further research is needed, we conducted a longitudinal observational study to report the prevalence and associated risk factors of the long-term health consequences of COVID-19 by symptom clusters in patients discharged from the Temporary COVID-19 Hospital (TCH) in Mexico City. Self-reported clinical symptom data were collected via telephone calls over 90 days post-discharge. Among 4670 patients, we identified 45 symptoms across eight symptom clusters (neurological; mood disorders; systemic; respiratory; musculoskeletal; ear, nose, and throat; dermatological; and gastrointestinal). RESULTS: We observed that the neurological, dermatological, and mood disorder symptom clusters persisted in >30% of patients at 90 days post-discharge. Although most symptoms decreased in frequency between day 30 and 90, alopecia and the dermatological symptom cluster significantly increased (p < 0.00001). Women were more prone than men to develop long-term symptoms, and invasive mechanical ventilation also increased the frequency of symptoms at 30 days post-discharge. CONCLUSION: Overall, we observed that symptoms often persisted regardless of disease severity. We hope these findings will help promote public health strategies that ensure equity in the access to solutions focused on the long-term consequences of COVID-19

PD-1 positive NK cell population is higher in patients with chronic lymphocytic leukaemia and contributes to the impaired function of NK cells

International Workshop on Chronic Lymphocytic Leukemia (17th. 2017. Nueva York

NK Cells in the Treatment of Hematological Malignancies

Natural killer (NK) cells have the innate ability to kill cancer cells, however, tumor cells may acquire the capability of evading the immune response, thereby leading to malignancies. Restoring or potentiation of this natural antitumor activity of NK cells has become a relevant therapeutic approach in cancer and, particularly, in hematological cancers. The use of tumor-specific antibodies that promote antibody-dependent cell-mediated cytotoxicity (ADCC) through the ligation of CD16 receptor on NK cells has become standard for many hematologic malignancies. Hematopoietic stem cell transplantation is another key therapeutic strategy that harnesses the alloreactivity of NK cells against cancer cells. This strategy may be refined by adoptive transfer of NK cells that may be previously expanded, activated, or redirected (chimeric antigen receptor (CAR)-NK cells) against cancer cells. The antitumor activity of NK cells can also be boosted by cytokines or immunostimulatory drugs such as lenalidomide or pomalidomide. Finally, targeting immunosubversive mechanisms developed by hematological cancers and, in particular, using antibodies that block NK cell inhibitory receptors and checkpoint proteins are novel promising therapeutic approaches in these malignant diseases

Ig-Like Transcript 2 (ILT2) Blockade and Lenalidomide Restore NK Cell Function in Chronic Lymphocytic Leukemia

One of the cardinal features of chronic lymphocytic leukemia (CLL) is its association with a profound immunosuppression. NK cell function is markedly impaired in CLL patients, who show a significant dysregulation of the expression of activating and inhibitory receptors. Here, we analyzed the role of the novel inhibitory receptor Ig-like transcript 2 (ILT2, also termed LIR-1, LILRB1) in the regulation of NK cells in CLL. Our results show that ILT2 expression was significantly decreased on leukemic cells and increased on NK cells of CLL patients, particularly in those with advanced disease and with bad prognostic features, such as those carrying chromosome del(11q). The immunomodulatory drug lenalidomide may regulate the expression of ILT2 and its ligands in CLL since it significantly increased the expression of ILT2 and partially reestablished the expression of its ligands on leukemic cells. Furthermore, lenalidomide significantly increased the activation and proliferation of NK cells, which was strongly enhanced by ILT2 blockade. Combining ILT2 blockade and lenalidomide activated NK cell cytotoxicity resulting in increased elimination of leukemic cells from CLL patients. Overall, we describe herein the role of an inhibitory receptor involved in the suppression of NK cell activity in CLL, which is restored by ILT2 blockade in combination with lenalidomide, suggesting that it may be an interesting therapeutic strategy to be explored in this disease

Lenalidomide and ILT2 blockade enhance NK cell function in chronic lymphocytic Leukemia

International Congress of Immunology (IUIS) (17th. 2019. Beijing, China