Enhancing anti-EGFRvIII CAR T cell therapy against glioblastoma with a paracrine SIRPγ-derived CD47 blocker.

A significant challenge for chimeric antigen receptor (CAR) T cell therapy against glioblastoma (GBM) is its immunosuppressive microenvironment, which is densely populated by protumoral glioma-associated microglia and macrophages (GAMs). Myeloid immune checkpoint therapy targeting the CD47-signal regulatory protein alpha (SIRPα) axis induces GAM phagocytic function, but CD47 blockade monotherapy is associated with toxicity and low bioavailability in solid tumors. In this work, we engineer a CAR T cell against epidermal growth factor receptor variant III (EGFRvIII), constitutively secreting a signal regulatory protein gamma-related protein (SGRP) with high affinity to CD47.

Proteome-based insights for IDH-mutant glioma classification.

In this issue, Bader et al. characterize the proteomes of diffuse glioma brain tumors by liquid chromatography mass spectrometry and classify isocitrate dehydrogenase (IDH)-mutant gliomas into two subtypes, which differ in oncogenic pathways and aerobic/anaerobic energy metabolism.

Cytokine Receptor Diversity in the Lamprey Predicts the Minimal Essential Cytokine Networks of Vertebrates.

The vertebrate adaptive immune systems (Agnatha and Gnathostomata) use sets of T and B lymphocyte lineages that somatically generate highly diverse repertoires of Ag-specific receptors and Abs. In Gnathostomata, cytokine networks regulate the activation of lymphoid and myeloid cells, whereas little is known about these components in Agnathans. Most gnathostome cytokines are four-helix bundle cytokines with poorly conserved primary sequences.

Near-exact treatment of seniority-zero ground and excited states with a Richardson-Gaudin mean-field.

Eigenvectors of the reduced Bardeen-Cooper-Schrieffer (BCS) Hamiltonian, Richardson-Gaudin (RG) states, are used as a variational wavefunction ansatz for strongly correlated electronic systems. These states are geminal products whose coefficients are solutions of non-linear equations. Previous results showed an un-physical apparent avoided crossing in ground state dissociation curves for hydrogen chains.

Microglia-Centered Combinatorial Strategies Against Glioblastoma.

Tumor-associated microglia (MG) and macrophages (MΦ) are important components of the glioblastoma (GBM) immune tumor microenvironment (iTME). From the recent advances in understanding how MG and GBM cells evolve and interact during tumorigenesis, we emphasize the cooperation of MG with other immune cell types of the GBM-iTME, mainly MΦ and T cells. We provide a comprehensive overview of current immunotherapeutic clinical trials and approaches for the treatment of GBM, which in general, underestimate the counteracting contribution of immunosuppressive MG as a main factor for treatment failure.