"Estadiaje de linfoma no Hodgkin: papel actual de la biopsia de médula ósea frente a nuevas técnicas diagnósticas"

La estadificación de de una neoplasia informa de su extensión y localización y aporta información sobre el manejo terapéutico y pronóstico. Se acepta para este papel la tecnología PET- TC, que aúna información metabólica y anatómica, empleándose ya de manera rutinaria en LH y LNH. La presencia de afectación medular ósea confiere al paciente un estadio IV y un peor pronóstico. Clásicamente se ha utilizado la biopsia de médula ósea para el estadiaje de la médula ósea en el linfoma no Hodgkin, a pesar de sus numerosas limitaciones y agresividad, por lo que se plantea su posible sustitución por PET-TC, manteniéndose la biopsia de médula ósea como un método complementario inestimable en determinados supuestos clínicos

Harnessing the potential of NK cell-based immunotherapies against multiple myeloma

Natural killer (NK) cell-based therapies have emerged as promising anticancer treatments due to their potency as cytolytic effectors and synergy with concurrent treatments. Multiple myeloma (MM) is an aggressive B-cell malignancy that, despite development of novel therapeutic agents, remains incurable with a high rate of relapse. In MM, the inhospitable tumor microenvironment prevents host NK cells from exerting their cytolytic function. The development of NK cell immunotherapy works to overcome this altered immune landscape and can be classified in two major groups based on the origin of the cell: autologous or allogeneic. In this review, we compare the treatments in each group, such as autologous chimeric antigen receptor (CAR) NKs and allogeneic off-the-shelf NK cell infusions, and their combinatorial effect with existing MM therapies including monoclonal antibodies and proteasome inhibitors. We also discuss their placement in clinical treatment regimens based on the immune profile of each patient. Through this examination, we would like to discover precisely when each NK cell-based treatment will produce the maximum benefit to the MM patient

Ecto-calreticulin expression in multiple myeloma correlates with a failed anti-tumoral immune response and bad prognosis

Immunogenic cell death (ICD) has been proposed to be a crucial process for antitumor immunosurveillance. ICD is characterized by the exposure and emission of Damage Associated Molecular Patterns (DAMP), including calreticulin (CRT). A positive correlation between CRT exposure or total expression and improved anticancer immunosurveillance has been found in certain cancers, usually accompanied by favorable patient prognosis. In the present study, we sought to evaluate CRT levels in the plasma membrane of CD38+ bone marrow mononuclear cells (BMMCs) isolated from 71 patients with varying degrees of multiple myeloma (MM) disease and examine the possible relationship between basal CRT exposure and the bone marrow immune microenvironment, as well as its connection with different clinical markers. Data show that increased levels of cell surface-CRT were associated with more aggressive clinical features and with worse clinical prognosis in MM. High CRT expression in MM cells was associated with increased infiltration of NK cells, CD8+ T lymphocytes and dendritic cells (DC), indicative of an active anti-tumoral immune response, but also with a significantly higher presence of immunosuppressive Treg cells and increased expression of PD-L1 in myeloma cells

Análisis de modelos de estratificación de riesgo en síndromes mielodisplásicos de bajo riesgo y su impacto en la toma de decisiones clínicas: Identifiación de subgrupos con evolución adversa

Los síndromes mielodisplásicos (SMD) son un grupo heterogéneo de enfermedades hematológicas caracterizados por una ineficacia de la médula ósea que conduce a diversas citopenias. Suele aparecer en personas de edad avanzada aunque los datos epidemiológicos son difíciles de recoger. La fisiopatología involucra numerosos procesos desde factores ambientales que favorecen su aparición, hasta factores genéticos, cuya investigación se encuentra en auge los últimos años con numerosos avances en la identificación de genes y mutaciones. Existen diversos sistemas pronósticos; y, a pesar de sus limitaciones, el IPSS es el más extendido en la actualidad. De esta manera, se catalogan en pacientes de bajo o alto riesgo, lo que conlleva un tratamiento u otro. Recientemente se ha descubierto que un pequeño grupo de los pacientes denominados de bajo riesgo, sufren un pronóstico peor de lo esperado, con una supervivencia mucho menor. La literatura actual trata de establecer cuáles son las características de esos pacientes para poder identificarlos, y que posibilidades de tratamiento podemos encontrar en la actualidad o deberíamos investigar en un futuro para un mejor manejo y reducción de la mortalidad: desde el uso de agentes hipometilantes hasta el trasplante de progenitores hematopoyéticos en etapas iniciales de la enfermedad

Harnessing the Potential of NK Cell-Based Immunotherapies against Multiple Myeloma

International audienceNatural killer (NK) cell-based therapies have emerged as promising anticancer treatments due to their potency as cytolytic effectors and synergy with concurrent treatments. Multiple myeloma (MM) is an aggressive B-cell malignancy that, despite development of novel therapeutic agents, remains incurable with a high rate of relapse. In MM, the inhospitable tumor microenvironment prevents host NK cells from exerting their cytolytic function. The development of NK cell immunotherapy works to overcome this altered immune landscape and can be classified in two major groups based on the origin of the cell: autologous or allogeneic. In this review, we compare the treatments in each group, such as autologous chimeric antigen receptor (CAR) NKs and allogeneic off-the-shelf NK cell infusions, and their combinatorial effect with existing MM therapies including monoclonal antibodies and proteasome inhibitors. We also discuss their placement in clinical treatment regimens based on the immune profile of each patient. Through this examination, we would like to discover precisely when each NK cell-based treatment will produce the maximum benefit to the MM patient

Human NK cells activated by EBV + lymphoblastoid cells overcome anti-apoptotic mechanisms of drug resistance in haematological cancer cells

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Expanded and activated allogeneic NK cells are cytotoxic against B-chronic lymphocytic leukemia (B-CLL) cells with sporadic cases of resistance

International audienceAdoptive transfer of allogeneic natural killer (NK) cells is becoming a credible immunotherapy for hematological malignancies. In the present work, using an optimized expansion/activation protocol of human NK cells, we generate expanded NK cells (eNK) with increased expression of CD56 and NKp44, while maintaining that of CD16. These eNK cells exerted significant cytotoxicity against cells from 34 B‑CLL patients, with only 1 sample exhibiting resistance. This sporadic resistance did not correlate with match between KIR ligands expressed by the eNK cells and the leukemic cells, while cells with match resulted sensitive to eNK cells. This suggests that KIR mismatch is not relevant when expanded NK cells are used as effectors. In addition, we found two examples of de novo resistance to eNK cell cytotoxicity during the clinical course of the disease. Resistance correlated with KIR‑ligand match in one of the patients, but not in the other, and was associated with a significant increase in PD‑L1 expression in the cells from both patients. Treatment of one of these patients with idelalisib correlated with the loss of PD‑L1 expression and with re‑sensitization to eNK cytotoxicity. We confirmed the idelalisib‑induced decrease in PD‑L1 expression in the B‑CLL cell line Mec1 and in cultured cells from B‑CLL patients. As a main conclusion, our results reinforce the feasibility of using expanded and activated allogeneic NK cells in the treatment of B‑CLL