Linfocitos B instruidos por bacterias potencian la capacidad citotóxica de linfocitos T CD8 naïve / [B lymphocytes instructed by bacteria enhance the cytotoxic capacity of naïve CD8 T lymphocytes]

Los linfocitos B desempeñan un papel bien conocido en la respuesta inmunitaria adaptativa, tanto a nivel humoral mediante la producción de anticuerpos y citoquinas como durante la activación de los linfocitos T CD4. Sin embargo, su capacidad para capturar, procesar y activar linfocitos T CD8 naïve mediante presentación cruzada (“cross-presentation”) es un campo en que los mecanismos moleculares que regulan dicha capacidad no están definidos. De forma previa, se sabía que las células B son capaces de incrementar las respuestas citotóxicas de linfocitos T CD8 durante la infección. En este trabajo recientemente publicado en EMBO Reports con Raquel García-Ferreras como primera autora, del laboratorio del Dr. Esteban Veiga en el Centro Nacional de biotecnología (CNB, Madrid), se demuestra cómo los linfocitos B capturan bacterias vía endocitosis a través de contactos con células dendríticas infectadas, siendo la transfagocitosis pues la vía preferida. Estos linfocitos B así instruidos procesan los componentes bacterianos mediante autofagia y presentan los antígenos producidos a linfocitos T CD8, que van a mejorar su capacidad citotóxica y por tanto su actividad para eliminar células diana. Para entender los mecanismos moleculares que regulan esto procesos los autores han utilizado diferentes modelos de ratón y cepas bacterianas derivadas de L monocytogenes, determinando mediante citometría de flujo y microscopía confocal la capacidad de presentación antigénica de los linfocitos B y la proliferación de los linfocitos T CD8. La transfagocitosis de dichas bacterias conlleva el uso de autofagia y esto ocurre mediante el aumento en la expresión de moléculas co-estimuladoras y del MHC-I y es dependiente de la autofagia no clásica. Las células CD8 citotóxicas entrenadas por los linfocitos B son así más efectivas en el reconocimiento de células tumorales que expresan antígenos específicos. ... (AU)

DC vaccine enhances CAR-T cell antitumor activity by overcoming T cell exhaustion and promoting T cell infiltration in solid tumors

Objective Great success has been achieved in CAR-T cell immunotherapy in the treatment of hematological tumors. However, it is particularly difficult in solid tumors, because CAR-T is difficult to enter interior and exert long-term stable immune effects. Dendritic cells (DCs) can not only present tumor antigens but also promote the infiltration of T cells. Therefore, CAR-T cells with the help of DC vaccines are a reliable approach to treat solid tumors. Methods To test whether DC vaccine could promote CAR-T cell therapy in solid tumors, DC vaccine was co-cultured with MSLN CAR-T cells. The in vitro effects of DC vaccine on CAR-T were assessed by measuring cell proliferation, cell differentiation, and cytokine secretion. Effects of DC vaccine on CAR-T were evaluated using mice with subcutaneous tumors in vivo. The infiltration of CAR-T was analyzed using immunofluorescence. The persistence of CAR-T in mouse blood was analyzed using real-time quantitative PCR. Results The results showed that DC vaccine significantly enhanced the proliferation potential of MSLN CAR-T cells in vitro. DC vaccines not only promoted the infiltration of CAR-T cells, but also significantly improved the persistence of CAR-T in solid tumors in vivo. Conclusion In conclusion, this study has demonstrated that DC vaccine can promote CAR-T therapy in solid tumors, which provides the possibility of widespread clinical application of CAR-T cells in the future (AU)

Chimeric antigen receptor T cells therapy in solid tumors

Chimeric antigen receptor T cells therapy (CAR-T therapy) is a class of ACT therapy. Chimeric antigen receptor (CAR) is an engineered synthetic receptor of CAR-T, which give T cells the ability to recognize tumor antigens in a human leukocyte antigen-independent (HLA-independent) manner and enables them to recognize more extensive target antigens than natural T cell surface receptor (TCR), resulting in tumor destruction. CAR-T is composed of an extracellular single-chain variable fragment (scFv) of antibody, which serves as the targeting moiety, hinge region, transmembrane spacer, and intracellular signaling domain(s). CAR-T has been developing in many generations, which differ according to costimulatory domains. CAR-T therapy has several limitations that reduce its wide availability in immunotherapy which we can summarize in antigen escape that shows either partial or complete loss of target antigen expression, so multiplexing CAR-T cells are promoted to enhance targeting of tumor profiles. In addition, the large diversity in the tumor microenvironment also plays a major role in limiting this kind of treatment. Therefore, engineered CAR-T cells can evoke immunostimulatory signals that rebalance the tumor microenvironment. Using CAR-T therapy in treating the solid tumor is mainly restricted by the difficulty of CAR-T cells infiltrating the tumor site, so local administration was developed to improve the quality of treatment. The most severe toxicity after CAR-T therapy is on-target/on-tumor toxicity, such as cytokine release syndrome (CRS). Another type of toxicity is on-target/off-tumor toxicity which originates from the binding of CAR-T cells to target antigen that has shared expression on normal cells leading to damage in healthy cells and organs. Toxicity management should become a focus of implementation to permit management beyond specialized centers (AU)

SUV39H1 is a prognosis and immune microenvironment-related biomarker in diffuse large B-cell lymphoma

Background The tumor microenvironment plays a crucial role in the oncogenesis and treatment of diffuse large B-cell lymphoma (DLBCL). The H3K9me3-specific histone methyltransferase Suppressor of variegation 3-9 homolog 1 (SUV39H1) is a significant gene that promotes the progression of various malignancies. However, the specific expression of SUV39H1 in DLBCL remains unclear. Methods By retrieving data from GEPIA, UCSC XENA and TCGA public databases, we observed the high expression of SUV39H1 in DLBCL. Combined with an immunohistochemical validation assay, we analyzed our hospital’s clinical characteristics and prognosis of 67 DLBCL patients. The results showed that high SUV39H1 expression was closely associated with age over 50 years (P = 0.014) and low albumin levels (P = 0.023) of patients. Furthermore, the experiments in vitro were deployed to evaluate the regulation of SUV39H1 on the DLBCL immune microenvironment. Results The results showed that high SUV39H1 expression was closely associated with age over 50 years (P = 0.014) and low albumin levels (P = 0.023) of patients. The prognostic analysis showed that the high SUV39H1 expression group had a lower disease-free survival (DFS) rate than the low SUV39H1 expression group (P < 0.05). We further discovered that SUV39H1 upregulated the expression of CD86+ and CD163+ tumor-associated macrophages by DLBCL patients’ tissues and cell experiments in vitro (P < 0.05). And SUV39H1-associated T lymphocyte subsets and cytokines IL-6/CCL-2 were downregulated in DLBCL (P < 0.05). Conclusions In summary, SUV39H1 might be not only a potential target for treating DLBCL but also a clinical indicator for doctors to evaluate the trend of disease development (AU)

Nuevos avances terapéuticos en pacientes con cáncer de pulmón inmunosuprimidos con enfermedades crónicas pulmonares en el periodo 2014-2022 a partir de la revisión de la literatura / New therapeutic advances in patients with lung cancer immunosuppressed with chronic lung diseases in the period 2014-2022 from the review of the literature

El cáncer de pulmón es una neoplasia maligna de gran prevalencia y mortalidad, más en pacientes con comorbilidades respiratorias,cuyas células tienen una capacidad de proliferación masiva en el tejido pulmonar logrando invadir otros órganos, deteriorando elestado físico y emocional del paciente, su calidad de vida y sistema de defensa. Además, el tratamiento no es suficiente hoy en díapara la supervivencia del paciente y se ha evidenciado cierta evolución en la terapéutica de la enfermedad o su detección precoz.El objetivo fue analizar los nuevos avances terapéuticos en pacientes con Cáncer de Pulmón asociado a enfermedades crónicaspulmonares en el periodo 2014-2022 a partir de la revisión de la literatura. Se aplicaron diversos parámetros para la limitación de bús-queda, extrapolando los artículos de interés, siendo validados cincuenta y tres artículos, seis tesis doctorales y dos libros, los cualeseran de idioma español e inglés. Las diversas estrategias de búsquedas usadas fueron las palabras claves, tema y seguimiento deautor. Los apartados desarrollados en la presente revisión fueron el concepto de cáncer de pulmón (CP), las manifestaciones clínicas,los factores de riesgo, la relación entre CP y enfermedades crónicas pulmonares, el diagnóstico, el tratamiento, la prevención y losnuevos avances terapéuticos. Toda la información filtrada de los artículos seleccionados nos pone de manifiesto la importancia queestá tomando el uso de diversos biomarcadores para su detección precoz; sin embargo, la transferencia de células T antitumoralesen pacientes con una enfermedad pulmonar de base presentó una eficiencia del 48%.(AU)

Lung cancer is a malignant neoplasm with a high prevalence and mortality, more so in patients with respiratory comorbidities, whosecells have a massive proliferation capacity in the lung tissue, managing to invade other organs, which deteriorates the patient’s phy-sical and emotional state, decreasing their quality of life and defense system; therefore, treatment today is not sufficient for patientsurvival and there has been evidence of a certain evolution in the treatment of the disease or early detection to prevent it. This articleaimed to analyze the new therapeutic advances in patients with lung cancer associated with chronic lung diseases in the period2014-2022 based on a review of the literature. Several parameters were used to limit the search, extrapolating the articles of interest,validating fifty three articles, six doctoral theses and two books, which were in Spanish and English.The various search strategiesused were keywords, subject and author follow-up. The sections developed in this review are the concept of Lung Cancer (LC), clinicalmanifestations, risk factors, relationship between LC and chronic lung diseases, diagnosis, treatment, prevention and new therapeuticadvances. All the filtered information of the selected articles shows us the importance that the use of various biomarkers is takingfor its early detection; however, the transfer of antitumor T cells in patients with underlying lung disease had an efficiency of 48%.(AU)

RNY3 modulates cell proliferation and IL13 mRNA levels in a T lymphocyte model: a possible new epigenetic mechanism of IL-13 regulation

Allergic asthma is the most common type of asthma. It is characterized by TH2 cell–driven inflammation in which interleukin-13 (IL-13) plays a pivotal role. Cytoplasmic RNAs (Y-RNAs), a variety of non-coding RNAs that are dysregulated in many cancer types, are also differentially expressed in patients with allergic asthma. Their function in the development of the disease is still unknown. We investigated the potential role of RNY3 RNA (hY3) in the TH2 cell inflammatory response using the Jurkat cell line as a model. hY3 expression levels were modulated to mimic the upregulation effect in allergic disease. We evaluated the effect of hY3 over cell stimulation and the expression of the TH2 cytokine IL13. Total RNA was isolated and retrotranscribed, and RNA levels were assessed by qPCR. In Jurkat cells, hY3 levels increased upon stimulation with phorbol 12-myristate 13-acetate (PMA) and ionomycin. When transfecting with high levels of hY3 mimic molecules, cell proliferation rate decreased while IL13 mRNA levels increased upon stimulation compared to stimulated control cells. Our results show the effect of increased hY3 levels on cell proliferation and the levels of IL13 mRNA in Jurkat cells. Also, we showed that hY3 could act over other cells via exosomes. This study opens up new ways to study the potential regulatory function of hY3 over IL-13 production and its implications for asthma development. (AU)

Overcome tumor relapse in CAR T cell therapy

Chimeric antigen receptor (CAR) T cell therapy is a novel therapeutic approach that uses gene editing techniques and lentiviral transduction to engineer T cells so that they can effectively kill tumors. However, CAR T cell therapy still has some drawbacks: many patients who received CAR T cell therapy and achieve remission, still had tumor relapse and treatment resistance, which may be due to tumor immune escape and CAR T cell dysfunction. To overcome tumor relapse, more researches are being done to optimize CAR T cell therapy to make it more precise and personalized, including screening for more specific tumor antigens, developing novel CAR T cells, and combinatorial treatment approaches. In this review, we will discuss the mechanisms as well as the progress of research on overcoming plans. (AU)

Commercialized kits to assess T-cell responses against SARS-CoV-2 S peptides. A pilot study in health care workers

BackgroundIt is crucial to assess the levels of protection generated by natural infection or SARS-CoV-2 vaccines, mainly in individuals professionally exposed and in vulnerable groups. Measuring T-cell responses may complement antibody tests currently in use as correlates of protection. Our aim was to assess the feasibility of a validated assay of T-cell responses.MethodsTwenty health-care-workers (HCW) were included. Antibody test to SARS-CoV-2 N and S-proteins in parallel with a commercially available whole-blood-interferon-gamma-release-assay (IGRA) to S-peptides and two detection methods, CLIA and ELISA were determined.ResultsIGRA test detected T-cell responses in naturally exposed and vaccinated HCW already after first vaccination dose. The correlation by the two detection methods was very high (R>0.8) and sensitivity and specificity ranged between 100 and 86% and 100-73% respectively. Even though there was a very high concordance between specific antibody levels and the IGRA assay in the ability to detect immune response to SARS-CoV-2, there was a relatively low quantitative correlation. In the small group primed by natural infection, one vaccine dose was sufficient to reach immune response plateau. IGRA was positive in one, with Ig(S) antibody negative vaccinated immunosuppressed HCW illustrating another advantage of the IGRA-test.ConclusionWhole-blood-IGRA-tests amenable to automation and constitutes a promising additional tool for measuring the state of the immune response to SARS-CoV-2; they are applicable to large number of samples and may become a valuable correlate of protection to COVID-19, particularly for vulnerable groups at risk of being re-exposed to infection, as are health-care-workers. (AU)

IntroducciónEs fundamental evaluar los niveles de protección inmune en infectados o tras la vacunación frente a SARS-CoV-2. La cuantificación de la respuesta inmune celular T puede complementar la determinación de anticuerpos. Evaluamos la viabilidad de un ensayo comercial validado de respuesta celular T específica frente a SARS-CoV-2.MétodosSe incluyeron veinte trabajadores sanitarios (TS). Medimos anticuerpos contra las proteínas N y S de SARS-CoV-2 y realizamos el ensayo de liberación de interferón-gamma (IFNγ) en sangre completa (IGRA) frente a péptidos de la proteína S. IFNγ se determinó mediante dos métodos de detección: CLIA y ELISA.ResultadosIGRA detectó respuesta celular T en TS tanto infectados como vacunados. La correlación de los dos métodos de detección de IFNγ fue muy alta (R>0,8) y la sensibilidad y la especificidad variaron entre 100 y 86% y 100-73% respectivamente. Hubo una concordancia muy alta entre los niveles de anticuerpos específicos y el ensayo IGRA aunque la correlación cuantitativa fue relativamente baja. En el grupo de infectados, una dosis de vacuna fue suficiente para alcanzar el «plateau» de respuesta inmune. IGRA fue claramente positivo en un profesional vacunado inmunosuprimido que presentaba anticuerpos contra la proteína S negativos.ConclusionesIGRA frente a péptidos de la proteína-S es susceptible de automatización y constituye una herramienta prometedora para medir la respuesta inmune celular frente a SARS-CoV-2; es aplicable a un gran número de muestras y puede servir para valorar la protección, particularmente en los grupos vulnerables en riesgo de volver a exponerse a la infección, como los TS. (AU)

Application of the diagnostic criteria for Common Variable Immunodeficiency in resource-limited settings

Introduction: Common variable immunodeficiency (CVID) is the most prevalent symptom-atic humoral deficiency; however, its heterogeneous presentation makes the diagnosis diffi-cult. The present study is aimed to verify the CVID diagnostic criteria as established by the European Society for Immunodeficiencies in 42 CVID patients from our outpatient clinic. Methods: Information was collected from their medical records and when needed, lymphocyte subpopulations in peripheral blood (PB) were performed by flow cytometry. Results: All the patients fulfilled the clinical working definition for CVID and showed decreased serum IgG and IgA at diagnosis. Over two-thirds of the patients had decreased memory B cell percentages. However, the remaining patients exhibited other quantitative B cell defects in PB. Evaluation of vaccination responses was only found in 13 records and 69% were not respon-sive. None of the patients were subjected to vaccination studies to both, T-cell dependent and independent antigens. The two required tests to evaluate T cell responses were performed in 84.2% of the patients and reported normal. Without the support of third-party payers, only 34.2% of our patients would have completed the required evaluations. Conclusions: Further efforts are needed to speed up CVID diagnosis in low-resourced settings, increasing the availability of the required resources and optimizing the healthcare supply chain (AU)

Identificación de la función de las células T en los microambientes del cáncer de pulmón

PurposeTo investigate whether γδ1 T cells derived from lung cancer tissues have immunosuppressive function and to verify the mechanism of immunosuppressive effect.MethodsFresh lung cancer tissue samples were collected, some of them were prepared tissue sections, the others were isolated and amplified into TILs cells, γδ1 T cells were isolated from TILs cells by immunomagnetic beads kits, and then cloned and amplified. The immunomodulatory effects of γδ1 T cells on naive and effector CD4+ T cells were detected by immunohistochemistry, flow cytometry, CCK8, ELISA and transwell culture.ResultsA high proportion of γδ1 T cells was found in lung cancer tissues. The cultural supernatants of γδ1 T cells could inhibit the proliferation of naive CD4+ T cells and decrease the secretion level of IL-2 by effector CD4+ T cells. Further studies showed that the expression levels of IL-8, MIP-1α, MIP-1β and RANTES were higher than that of IFN-γ, GM-CSF and TNF-α, TNF-β, however, their neutralizing antibodies could not block the immunosuppressive activity of the supernatant.Conclusionγδ1 T cells play an negative immunoregulation function in lung cancer microenvironments, and have obvious immunosuppressive effects on proliferation and cytokine release of naive CD4+ T cells and effector CD4+ T cells. Preliminary evidence from this study suggests that the mechanism of immunosuppressive effects is mediated by the soluble factors in γδ1 T cell culture supernatants, but its exact molecular mechanism needs to be further explored.

Role of Soluble T-Cell Immunoglobulin Mucin Domain-3 in Differentiating Nontuberculous Mycobacterial Lung Disease from Pulmonary Colonization

Background: Differentiating between nontuberculous mycobacterial lung disease (NTM-LD) and pulmonary NTM colonization (NTM-Col) is difficult. Compared with healthy controls, patients with NTM-LD generally present immune tolerance along with increased expressions of T-cell immunoglobulin mucin domain-3 (TIM-3) and programmed cell death-1 (PD-1) on T lymphocytes. However, the role of soluble TIM-3 (sTIM-3) and soluble PD-1 (sPD-1) in differentiating NTM-LD from NTM colonization (NTM-Col) remains unclear. Methods: Patients with NTM-positive respiratory samples and controls were enrolled from 2016 to 2019. Patients were classified into NTM-Col and NTM-LD groups. Levels of sTIM-3, sPD-1, soluble PD-ligand-1 (sPD-L1), and TIM-3 expression were measured. Factors associated with NTM-LD were analyzed by logistical regression. Results: TIM-3 expression on CD4+ and CD8+ T lymphocytes were highest in NTM-LD group, followed by NTM-Col, and control (P=.017 and P=.011 for trend). sTIM-3 elevated in the NTM-Col group compared with the NTM-LD and control groups (856.3±518.7 vs. 595.3±352.6pg/mL, P=.009; vs. 437.0±267.4pg/mL, P<.001). Levels of soluble PD-1 and its ligand were similar among groups. Among the 79 NTM-positive patients, sTIM-3 was associated with NTM-LD (100-pg/mL increase, adjusted odds ratio (aOR) 0.658 [95% CI, 0.502–0.864], P=.003). Patients with ≥2 risk factors (sTIM-3≤530pg/mL, BMI≤22.5, and radiographic score ≥5) were 13 times more likely to exhibit NTM-LD than those without (aOR 13.234 [2.983–58.709], P=.001). Conclusions: sTIM-3 was an independent factor for differentiating NTM-LD from NTM-Col, suggesting the immunologic role of sTIM-3 in NTM-LD pathogenesis. By assessing sTIM-3 levels and other risk factors, physicians may be able to identify NTM-LD cases in a simplified manner. (AU)

Terapia con linfocitos T con receptor de antígeno quimérico (CAR-T) en pacientes con linfoma de célula B agresivo. Perspectiva actual tras una década de tratamiento / Chimeric antigen receptor T-cell (CAR-T) therapy in patients with aggressive B-cell lymphomas. Current outlook after a decade of treatment

La terapia con linfocitos T con receptor de antígeno quimérico (CAR-T) ha revolucionado el manejo de los pacientes con linfoma difuso de células grandes B (LDCGB) refractarios o en recaída tras inmunoquimioterapia. Esta estrategia consiste en modificar genéticamente los linfocitos T de los propios pacientes para favorecer el reconocimiento de los antígenos tumorales seleccionados. Actualmente, hay disponibles dos medicamentos CAR-T anti-CD19 aprobados en España para pacientes con LDCGB tras dos o más líneas de tratamiento sistémico previo y existen múltiples ensayos clínicos en marcha que investigan su uso en líneas de tratamiento más precoces. Tanto los ensayos clínicos pivotales como los datos de práctica asistencial poscomercialización han contribuido a definir el perfil de eficacia y seguridad de cada constructo, a identificar los principales factores pronósticos de respuesta y a optimizar el manejo de las distintas fases de esta terapia. Todos estos aspectos se repasan en esta revisión. (AU)

Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the management of patients with diffuse large B-cell lymphoma (DLBCL) who are refractory or relapse after immunochemotherapy. This strategy consists in genetically modifying the patient's own T lymphocytes to favor the recognition of selected tumor antigens. Currently, we have two anti-CD19 CAR-T drugs approved in Spain for patients with DLBCL after two or more prior treatment lines and there are multiple ongoing clinical trials exploring earlier lines of treatment. Both clinical trials and post-marketing real-world data have contributed to better define the efficacy and safety profile of each construct, identifying the main prognostic response factors and improving the management of each step in this therapy. All these aspects are reviewed herein. (AU)

Patients With Atopic Dermatitis Sensitized to Pet Dander Mount IgE and T-Cell Responses to Mammalian Cystatins, Including the Human Self-Protein

Background: Immediate and delayed-type hypersensitivity reactions to pet-borne allergens are common in atopic diseases. In atopic dermatitis (AD), controversy surrounds the contribution to the disease of cross-reactivity to self-proteins. Human cystatin A and the cat allergen Fel d 3 belong to the cystatins, an evolutionary conserved protein family. The objective of the present study was to assess crossreactivity between mammalian cystatins and to analyze T-cell responses to cystatin in AD patients sensitized to pet dander. Methods: cDNA coding for dog cystatin was cloned from dog skin. Sera from 245 patients with IgE-mediated sensitization to cat and dog dander were tested for IgE binding to recombinantly expressed feline, canine, and human cystatin. Of these, 141 were also diagnosed with AD. Results: Cystatin-specific IgE was detected in 36 patients (14.7%), of whom 19 were considerably affected by AD. Within the AD patients, 9 had measurable IgE against all 3 cystatins. Cystatin-sensitized AD patients did not differ from non–cystatin-sensitized patients in terms of disease severity, age, or total IgE levels. T-cell cytokine measurements showed elevated IL-4 levels after stimulation with feline and human cystatin. Conclusion: The humoral response suggests that in addition to Fel d 3, the homologous protein from dog might play a role in allergy. Furthermore, human cystatin appears to be capable of driving a type 2 immune response in sensitized AD patients and may therefore be considered a so-called autoallergen, as proposed for other evolutionary conserved proteins. (AU)

Antecedentes: Las reacciones de hipersensibilidad de tipo inmediato y retardado a los alérgenos que están en las mascotas son comunes en las enfermedades atópicas. En este estudio, en pacientes con dermatitis atopica (DA), se analiza la reactividad cruzada con las autoproteínas y su contribución a la enfermedad. Tanto la cistatina A humana como el alérgeno felino Fel d 3 pertenecen a la familia de las cistatinas, una familia de proteínas conservadas evolutivamente. El objetivo del presente estudio fue evaluar la reactividad cruzada entre las cistatinas de mamíferos y analizar la respuestas de las células T a la cistatina en pacientes con DA sensibilizados a la caspa de las mascotas. Métodos: El ADNc que codifica la cistatina de perro se clonó a partir de piel de perro. Se analizaron sueros de 245 pacientes con sensibilización por IgE a la caspa de gato y perro para determinar la unión de IgE a cistatina felina, canina y humana expresada de forma recombinante, respectivamente. De estos 245 pacientes, 141 fueron diagnosticados de DA. Resultados: Se detectó IgE específica frente a cistatina en el 14,7% (36) de los pacientes, de los cuales 19 padecían DA. Dentro de los pacientes con DA, 9 tenían IgE medible contra las tres cistatinas. Los pacientes con DA sensibilizados frente a cistatina no difirieron de los pacientes no sensibilizados con cistatina en términos de gravedad de la enfermedad, edad o niveles totales de IgE. El análisis de citocinas de células T reveló niveles elevados de IL-4 después de la estimulación con cistatina felina y humana. Conclusión: La respuesta humoral sugiere que, además de Fel d 3, la proteína homóloga de perro también podría desempeñar un papel en la alergia. Además, la cistatina humana parece ser capaz de promover una respuesta inmune de tipo 2 en pacientes con DA sensibilizados y, por lo tanto, puede considerarse un autoalérgeno, como se ha propuesto para otras proteínas conservadas evolutivamente. (AU)

Characterization of a xenograft model for anti-CD19 CAR T cell studies

Purpose Chimeric antigen receptor (CAR) T cell development for B cell malignancies treatment has triggered a paradigm shift in oncology. The development of anti-CD19 CAR T cells relies primarily on a panel of cell line-derived xenograft models, including Raji cells; however, the behavior of this model is under debate. We attempted to characterize this lymphoma model and propose outcome measures for CAR T cell studies Methods Raji cell line was inoculated into NOG mice via intra-venous (IV), intra-peritoneal (IP), and subcutaneous (SC) routes with different inoculum sizes, and consequent clinical and histopathological outcomes were assessed. Results Inoculum sizes of 105–106 resulted in a complete take rate. The mice with IV and SC-inoculated Raji cells presented the shortest and longest survival among lymphoma-bearing mice, respectively (P < 0.01). The IP group had the highest number of both infiltrated organs (P < 0.05; compared to SC) and involvement of lymphatic sites (P < 0.05; compared to IV). The number of lymphoma lesions on the liver was higher in the IV compared to IP (P < 0.001) and SC (P < 0.05). Conclusion We demonstrate that the Raji cell line inoculation route could determine the xenograft model system behavior in terms of survival, tumor burden, and dissemination pattern and gives the model the specific features suitable for testing the specific hypothesis in CAR T cell therapy. We also conclude outcome measures for CAR T cell studies that do not require imaging techniques (AU)