Targeting ADCC: A different approach to HER2 breast cancer in the immunotherapy era

The clinical outcome of patients with human epidermal growth factor receptor 2 (HER2) amplified breast carcinoma (BC) has improved with the development of anti-HER2 targeted therapies. However, patients can experience disease recurrence after curative intent and disease progression in the metastatic setting. In the current era of evolving immunotherapy agents, the understanding of the immune response against HER2 tumor cells developed by anti-HER2 antibodies (Abs) is rapidly evolving. Trastuzumab therapy promotes Natural Killer (NK) cell activation in patients with BC overexpressing HER2, indicating that the efficacy of short-term trastuzumab monotherapy, albeit direct inhibition of HER, could also be related with antibody-dependent cell-mediated cytotoxicity (ADCC). Currently, dual HER2 blockade using trastuzumab and pertuzumab is the standard of care in early and advanced disease as this combination could confer an additive effect in ADCC. In patients with disease relapse or progression, ADCC may be hampered by several factors such as FcγRIIIa polymorphism and an immunosuppressive environment, among others. Hence, new drug development strategies are being investigated aiming to boost the ADCC response triggered by anti-HER2 therapy. In this review, we summarize these strategies and the rationale, through mAbs engineering and combinatorial strategies, focusing on clinical results and ongoing trials.Fil: Mandó, Pablo. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; ArgentinaFil: Rivero, Sergio G.. Instituto Alexander Fleming.; ArgentinaFil: Rizzo, Manglio Miguel. Universidad Austral. Hospital Universitario Austral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pinkasz, Marina. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Levy, Estrella Mariel. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Peripheral changes in immune cell populations and soluble mediators after anti-PD-1 therapy in non-small cell lung cancer and renal cell carcinoma patients

Patients with non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) have shown benefit from anti-PD-1 therapies. However, not all patients experience tumor shrinkage, durable responses or prolonged survival, demonstrating the need to find response markers. In blood samples from NSCLC and RCC patients obtained before and after anti-PD-1 treatment, we studied leukocytes by complete blood cell count, lymphocyte subsets using flow cytometry and plasma concentration of nine soluble mediators, in order to find predictive biomarkers of response and to study changes produced after anti-PD-1 therapy. In baseline samples, discriminant analysis revealed a combination of four variables that helped differentiate stable disease-response (SD-R) from progressive disease (PD) patients: augmented frequency of central memory CD4+ T cells and leukocyte count was associated with response while increased percentage of PD-L1+ natural killer cells and naïve CD4+ T cells was associated with lack of response. After therapy, differential changes between responders and non-responders were found in leukocytes, T cells and TIM-3+ T cells. Patients with progressive disease showed an increase in the frequency of TIM-3 expressing CD4+ and CD8+ T cells, whereas SD-R patients showed a decrease in these subsets. Our findings indicate that a combination of immune variables from peripheral blood (PB) could be useful to distinguish response groups in NSCLC and RCC patients treated with anti-PD-1 therapy. Frequency of TIM-3+ T cells showed differential changes after treatment in PD vs SD-R patients, suggesting that it may be an interesting marker for monitoring progression during therapy.Fil: Juliá, Estefanía Paula. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mandó, Pablo. Fundación Cáncer. Centro de Investigaciones Oncológicas; ArgentinaFil: Rizzo, Manglio Miguel. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cueto, Gerardo Ruben. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Tsou, Florencia. Instituto Alexander Fleming; ArgentinaFil: Luca, Romina. Fundación Cáncer. Centro de Investigaciones Oncológicas; ArgentinaFil: Pupareli, Carmen. Instituto Alexander Fleming; ArgentinaFil: Bravo, Alicia Inés. Gobierno de la Provincia de Buenos Aires. Hospital Interzonal General de Agudos Presidente Peron; ArgentinaFil: Astorino, Walter. Instituto Alexander Fleming; ArgentinaFil: Mordoh, José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Martín, Claudio. Instituto Alexander Fleming; ArgentinaFil: Levy, Estrella Mariel. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

High neutrophil to lymphocyte ratio and decreased CD69+NK cells represent a phenotype of high risk in early-stage breast cancer patients

Purpose: Breast cancer (BC) is a highly heterogeneous disease presenting a broad range of clinical and molecular characteristics. In the past years, a growing body of evidence demonstrated that immune response plays a significant role in cancer outcome. However, immune prognostic markers are not completely validated in clinical practice in BC patients. Materials and methods: With the aim to characterize immune features, several parameters were analyzed in peripheral blood at diagnosis of 85 nonmetastatic BC patients between April 2011 and July 2014. Results: With a median follow-up of 38.6 months, peripheral blood analysis of BC patients (stages I, II, and III) showed that total lymphocyte and T lymphocyte counts were augmented in nonrelapsed patients. Also, a higher neutrophil-to-lymphocytes ratio was associated with prolonged disease-free survival. Natural killer cell receptor analysis revealed that early activation receptor CD69 was associated with a better outcome. Conclusion: This preliminary evidence is in accordance with the concept of immune surveillance. We suggest an “immune phenotype” that provides relevant prognostic information in early-stage BC patients and which could be useful in the decision-making process.Fil: Mandó, Pablo. Oncology Research Center; ArgentinaFil: Rizzo, Manglio Miguel. Instituto Alexander Fleming; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Roberti, María Paula. Oncology Research Center; ArgentinaFil: Juliá, Estefanía Paula. Oncology Research Center; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pampena, María Betina. Oncology Research Center; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: de la Puente, Constanza Pérez. Instituto Alexander Fleming; ArgentinaFil: Loza, Carlos Martín. Instituto Alexander Fleming; ArgentinaFil: Ponce, Carolina. Instituto Alexander Fleming; ArgentinaFil: Nadal, Jorge. Instituto Alexander Fleming; ArgentinaFil: Coló, Federico Andres. Instituto Alexander Fleming; ArgentinaFil: Mordoh, José. Oncology Research Center; ArgentinaFil: Levy, Estrella Mariel. Instituto Alexander Fleming; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Prevalence of hepatitis E virus in children from Northeast of Argentina

The aim of this study was to assess the prevalence of hepatitis E virus (HEV) in a young population from the Northeast region of Argentina. Four hundred and twelve patients under 18 years old, from rural areas of Chaco Province, were tested for anti-HEV immunoglobulin G (IgG) using enzyme-linked immunosorbent assay. Anti-HEV IgG antibodies were detected in 7 out of 412 patients, accounting for an overall 1.7% prevalence. HEV infection in developing countries is associated to lack of clean drinking water. Consequently, the seroprevalence observed in children in rural areas of Chaco, Argentina, where the access to tap water is less than 15%, was unexpectedly low.Fil: Martínez, Alfredo P.. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; ArgentinaFil: Pereson, Matías J.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; ArgentinaFil: Pérez, Paula Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Baeck, María Inés. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; ArgentinaFil: Mandó, Pablo. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; ArgentinaFil: López Saubidet, Ignacio. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; ArgentinaFil: Di Lello, Federico Alejandro. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin

Lack of Prognostic Value of Pretreatment Neutrophil-to-Lymphocyte Ratio in Early Breast Cancer

Background: Breast cancer is a highly heterogeneous disease with large differences in the risk of recurrence. An elevated neutrophil-to-lymphocyte ratio (NLR) is correlated with a poor prognosis in a variety of tumors, and although it is still controversial in breast cancer, there are multiple studies, including meta-analysis, suggesting this. The purpose of this study was to analyze the prognostic value of preoperative NLR in an Argentine population of patients with nonmetastatic breast cancer, not exposed to neoadjuvant treatment. Methods: Retrospective multicenter cohort study that includes patients over 18 years of age from three centers in the city and province of Buenos Aires who have had surgery for early breast cancer between January 1, 1999, and December 31, 2014. Based on the previous literature, a cutoff value of 2.0 was defined. Results: A total of 791 patients were eligible for the analysis. Median age was 55 years (IQR 45-65). Median NLR was 1.92 (IQR 1.50-2.56). The distribution of groups according to the 8th edition of the AJCC was 54.1% for stage I, 35.6% stage II, and 10.4% stage III. Among the different tumor phenotypes, 79.0% were HR+/HER2-, 11.4% were HR+ or-/HER2+, and 9.2% were HR-/HER2-. With a median follow-up of 5.3 years, 112 patients (14.2%) had disease recurrence. Stage III patients had a higher NLR than stage I and stage II patients (p = 0.002). The rest of the clinical and pathological characteristics did not show differences in the groups according to NLR. There were no differences in relapse-free survival according to the NLR (p = 0.37), and itdid not change after adjusting for other prognostic variables. Conclusion: We consider it is important to determine the efficacy of prognostic markers that are easily accessible and of simple, systematic application. However, NLR does not appear to be an independent prognostic factor for recurrence in our population. In this sense, we consider it is important to publish negative results in order to avoid publication bias.Fil: Sifón, Maria Del Rosario. Centro de Educación Medica E Invest.clinicas; ArgentinaFil: Marcolini, Nicolas. Universidad Austral; ArgentinaFil: Barber, Maria Julia. Universidad Austral; ArgentinaFil: McLean, Ignacio. Universidad Austral; ArgentinaFil: Rizzo, Manglio Miguel. Universidad Austral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rivero, Sergio. Instituto Alexander Fleming; ArgentinaFil: Costanzo, Maria Victoria. Instituto Alexander Fleming; ArgentinaFil: Nervo, Adrian. Instituto Alexander Fleming; ArgentinaFil: Crimi, Gabriel. Centro de Educación Medica E Invest.clinicas; ArgentinaFil: Perazzo, Florencia. Centro de Educación Medica E Invest.clinicas; ArgentinaFil: Levy, Estrella Mariel. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mandó, Pablo. Centro de Educación Medica E Invest.clinicas; Argentin

A brief report of Covid-19 Cases In Cancer Patients from AMBA: Description of hospitalized population and their immunity against Sars-Cov-2

BACKGROUND: Until today there are registered 229,414,751cases and 4,707,872 deaths attributable to the disease caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) called COVID-19, all over the world. COVID-19 can be asymptomatic or causing a respiratory distress syndrome and death. The risk of COVID-19 and mortality for COVID-19 have been associated with older age and comorbidities, such as cancer. The situation is a great challenge for these patients. Furthermore, in patients with active treatment, the decrease in cell populations involved in protection is very common and immunity against SARS-CoV-2 may be impaired. OBJECTIVES: Here we described the population of oncological (P On) and non-oncological (P NOn) patients with moderate or severe COVID-19 hospitalized at the HUA from December, 2020 to September, 2021. Peripheral blood samples were collected at different times to analyze the duration of the protective response (Elisa; flow cytometry) RESULTS: We incorporated 24 patients: 11 [45%] with oncological disease in treatment, 5 male median age 59 with lung (4) and scalp (1) cancer and 6 female median age 36 with ovarian (1), cervix (2), renal (1) rectum (1) and breast cancer (1) with moderate (9) or severe (2) COVID-19 and 13 patients without oncological disease [54%], 7 male median age 59 years, 6 female median age 40, with moderate (12) or severe (1) COVID-19. In addition, the POn group had a longer hospital stay (15.9 vs 8.8 days; p 0.016); higher oxygen requirement (high flow 36.4% vs 7.7%; p 0.085). The mortality rate in POn was 36% and there were no deaths in PNon. The circulating immune response for SARS-CoV-2 was analyzed in 50 samples at different times from the 24 hospitalized patients. The protective response was significantly lower in the POn population (p <0.001) with low detection of IgM and IgG. CONCLUSIONS: in POn the protective response is lower compared to PNon, with probable implications in morbidity and mortality.Fil: Díaz, Marco A.. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Fusco, Mariel Alejandra. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Picón, Carlos Rafael. Universidad Austral. Hospital Universitario Austral. Departamento de Medicina Interna. Servicio de Oncologia.; ArgentinaFil: Bezazián, Ana. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Marcolini, Nicolás. Universidad Austral. Hospital Universitario Austral. Departamento de Medicina Interna. Servicio de Oncologia.; ArgentinaFil: Alvarez, Laura. Universidad Austral. Hospital Universitario Austral. Departamento de Diagnostico y Tratamiento. Servicio de Laboratorio.; ArgentinaFil: Brenzoni, Pablo. Universidad Austral. Hospital Universitario Austral. Departamento de Diagnostico y Tratamiento. Servicio de Laboratorio.; ArgentinaFil: Fiore, Esteban Juan. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Rosello, Paula Luciana. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Mandó, Pablo. Centro de Educaciones Médicas e Investigación Clínica "Norberto Quirno"; ArgentinaFil: Kostianovsky, Alex. Centro de Educaciones Médicas e Investigación Clínica "Norberto Quirno"; ArgentinaFil: Bizantino, Guillermo. Universidad Austral. Hospital Universitario Austral. Areas de Responsabilidad. Emergencias.; ArgentinaFil: Rodriguez, Marcelo. Universidad Austral. Hospital Universitario Austral. Areas de Responsabilidad. Emergencias.; ArgentinaFil: Baña, Matias Tisi. Universidad Austral. Hospital Universitario Austral. Departamento de Medicina Interna.; ArgentinaFil: Silva, Carlos. Universidad Austral. Hospital Universitario Austral. Departamento de Medicina Interna. Servicio de Oncologia.; ArgentinaFil: Hansen, Diana. Walter and Eliza Hall Institute of Medical Research; AustraliaFil: Malvicini, Matiana. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaLXVI Reunión Anual De La Sociedad Argentina De Investigación Clínica (Saic), LXIX Reunión Anual De La Sociedad Argentina De Inmunología (Sai), LIII Reunión Anual De La Asociación Argentina De Farmacología Experimental (Aafe) y XI Reunión Anual De La Asociación Argentina De Nanomedicinas (Nanomed-Ar)Buenos AiresArgentinaSociedad Argentina De Investigación ClínicaSociedad Argentina De InmunologíaAsociación Argentina De Farmacología ExperimentalAsociación Argentina De Nanomedicina

High neutrophil to lymphocyte ratio and decreased CD69⁺NK cells represent a phenotype of high risk in early-stage breast cancer patients

Purpose: Breast cancer (BC) is a highly heterogeneous disease presenting a broad range of clinical and molecular characteristics. In the past years, a growing body of evidence demonstrated that immune response plays a significant role in cancer outcome. However, immune prognostic markers are not completely validated in clinical practice in BC patients. Materials and methods: With the aim to characterize immune features, several parameters were analyzed in peripheral blood at diagnosis of 85 nonmetastatic BC patients between April 2011 and July 2014. Results: With a median follow-up of 38.6 months, peripheral blood analysis of BC patients (stages I, II, and III) showed that total lymphocyte and T lymphocyte counts were augmented in nonrelapsed patients. Also, a higher neutrophil-to-lymphocytes ratio was associated with prolonged disease-free survival. Natural killer cell receptor analysis revealed that early activation receptor CD69 was associated with a better outcome. Conclusion: This preliminary evidence is in accordance with the concept of immune surveillance. We suggest an “immune phenotype” that provides relevant prognostic information in early-stage BC patients and which could be useful in the decision-making process.Fil: Mandó, Pablo. Oncology Research Center; ArgentinaFil: Rizzo, Manglio Miguel. Instituto Alexander Fleming; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Roberti, María Paula. Oncology Research Center; ArgentinaFil: Juliá, Estefanía Paula. Oncology Research Center; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pampena, María Betina. Oncology Research Center; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: de la Puente, Constanza Pérez. Instituto Alexander Fleming; ArgentinaFil: Loza, Carlos Martín. Instituto Alexander Fleming; ArgentinaFil: Ponce, Carolina. Instituto Alexander Fleming; ArgentinaFil: Nadal, Jorge. Instituto Alexander Fleming; ArgentinaFil: Coló, Federico Andres. Instituto Alexander Fleming; ArgentinaFil: Mordoh, José. Oncology Research Center; ArgentinaFil: Levy, Estrella Mariel. Instituto Alexander Fleming; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Young oncologists’ perspective on the role and future of the clinician-scientist in oncology

SCOPUS: ed.jinfo:eu-repo/semantics/publishe