Anti COVID-19 immunity developed as assessed in a community-based oncological center

Introduction: Serology (antibody) tests for the SARS-CoV-2 have been proposed as an instrument to inform health authorities about immunization during the COVID-19 pandemic. As there is a significant part of the population that may have some degree of immunity, it is of great interest to communicate the immunization results obtained in the first 500 healthcare workers (HCW), patients and relatives tested in a community-based Oncological Center. Materials and methods: Between April 9th, 2020 and May 8th, 2020, a group of healthcare workers (HCW), their families, and general public who had had the COVID-19 or had been in close contact with confirmed cases of COVID-19 were screened for IgG SARS-CoV-2 antibodies. The tests were carried out in a rigorous manner, strictly following the guidelines approved by the Spanish Ministry of Health (Ministerio de Sanidad). Results: The major objective of this study was to determine the proportion of asymptomatic infected individuals and those who had already secreted IgG against SARS-CoV-2 in our cancer treatment center or in the community of Barcelona. Patients were tested with PCR, Rapid diagnostic test (RDT) or enzyme-linked immunoabsorbent assay (ELISA). A total of 521 participants were tested, 206 with RDT and 315 with ELISA, 59 (11,32%) resulted positive to SARS-CoV-2. Conclusion: RDT and ELISA proved to be effective and sensible enough to determine the extent of SARS-CoV-2 immunization in a community-based oncological center. The degree of immunization reached is nowadays far away from what can be considered desirable for a herd immunization

Exploiting Canonical TGFβ Signaling in Cancer Treatment.

TGFβ is a pleiotropic cytokine that plays critical roles to define cancer cell phenotypes, construct the tumor microenvironment, and suppress antitumor immune responses. As such, TGFβ is a lynchpin for integrating cancer cell intrinsic pathways and communication among host cells in the tumor and beyond that together affect responses to genotoxic, targeted, and immune therapy. Despite decades of preclinical and clinical studies, evidence of clinical benefit from targeting TGFβ in cancer remains elusive. Here, we review the mechanisms by which TGFβ acts to oppose successful cancer therapy, the reported prognostic and predictive value of TGFβ biomarkers, and the potential impact of inhibiting TGFβ in precision oncology. Paradoxically, the diverse mechanisms by which TGFβ impedes therapeutic response are a principal barrier to implementing TGFβ inhibitors because it is unclear which TGFβ mechanism is functional in which patient. Companion diagnostic tools and specific biomarkers of TGFβ targeted biology will be the key to exploiting TGFβ biology for patient benefit

Validation of Anticorrelated TGFβ Signaling and Alternative End-Joining DNA Repair Signatures that Predict Response to Genotoxic Cancer Therapy.

PurposeLoss of TGFβ signaling increases error-prone alternative end-joining (alt-EJ) DNA repair. We previously translated this mechanistic relationship as TGFβ and alt-EJ gene expression signatures, which we showed are anticorrelated across cancer types. A score representing anticorrelation, βAlt, predicts patient outcome in response to genotoxic therapy. Here we sought to verify this biology in live specimens and additional datasets.Experimental designHuman head and neck squamous carcinoma (HNSC) explants were treated in vitro to test whether the signatures report TGFβ signaling, indicated by SMAD2 phosphorylation, and unrepaired DNA damage, indicated by persistent 53BP1 foci after irradiation or olaparib. A custom NanoString assay was implemented to analyze the signatures' expression in explants. Each signature gene was then weighted by its association with functional responses to define a modified score, βAltw, that was retested for association with response to genotoxic therapies in independent datasets.ResultsMost genes in each signature were positively correlated with the expected biological response in tumor explants. Anticorrelation of TGFβ and alt-EJ signatures measured by NanoString was confirmed in explants. βAltw was significantly (P < 0.001) better than βAlt in predicting overall survival in response to genotoxic therapy in The Cancer Genome Atlas (TCGA) pancancer patients and in independent HNSC and ovarian cancer patient datasets.ConclusionsAssociation of the TGFβ and alt-EJ signatures with their biological response validates TGFβ competency as a key mediator of DNA repair that can be readily assayed by gene expression. The predictive value of βAltw supports its development to assist in clinical decision making