Research articles

Here the authors show that, in mouse tumors, CD8⁺ T cells with a low-avidity TCR are the mediators of antitumor and immunotherapy responses, in part because T cells with a high-avidity TCR are more exhausted.

Adoro and colleagues report the involvement of the IRE1α–XBP1 signaling axis in protecting hematopoietic stem and progenitor cells from proteomic stress and as a safeguard against leukemic transformation.

Divangahi and colleagues report that β-glucan pretreatment before influenza A virus challenge can increase survival by inducing long-term reprogramming of neutrophils, promoting disease tolerance irrespective of viral load.

Dotti and colleagues performed an unbiased, high-throughput screen of kinase inhibitors to identify a three-kinase inhibitor cocktail capable of preserving a stem-cell-like subset in chimeric antigen receptor T cells.

Here the authors show that PCIF1 can regulate CD8⁺ T cell antitumor responses in mice and use this information to enhance chimeric antigen receptor T cell design.

Pulendran and colleagues define a molecular signature that can be used to predict the durability of antibody responses to vaccination and reveal important insights into the mechanisms by which vaccines induce durable immunity.

Here, Fry and colleagues examine the impact of antigen experience on subsequent CD8⁺ CAR T cell activity during the antileukemia response and show that RUNX2 overexpression enhances antitumor activity of these cells.

Blander and colleagues report a homeostatic regulatory effect played by inflammasomes in the bone marrow stromal compartment that suppresses premalignant stages of lymphomagenesis.

Here the authors dissect the contribution of IL-21 signaling to immune checkpoint-responding CD8⁺ T cells from mouse models and patients being treated for advanced melanoma.

Pyroptotic cell death results in inflammation. Here the authors find that F-actin-rich structures formed during macrophage pyroptosis persist after cell death to activate dendritic cells.

Tumor-antigen-specific CD8⁺ T cells are generally thought to help fight against cancer, but here the authors identify a subpopulation of CD8⁺ T cells that are associated with a poor clinical outcome in melanoma. Although these cells can recognize tumor antigens, they suppress cancer immunity.

Why joints are highly responsive to systemic inflammation is unknown. Hasegawa et al. sought to address this question, developing a whole-mount imaging system of the entire synovium to profile the vascular, neuronal and immune components.

Here, the authors show that signal transducer and activator of transcription 3 (STAT3) has dual functions in small cell lung cancer as its deletion inhibited primary tumor growth but boosted metastatic spread. These seemingly opposing functions are a result of the requirement of STAT3 for stimulator of interferon genes–interferon signaling in metastasis and the authors show how it can be targeted in mice.

Ley and colleagues show that negative selection only partially explains the difference between CD4⁺ T cell responses to self and foreign peptides and that PD-1 and CD73 synergistically limit the CD4⁺ T cell responses to self.

Wang and colleagues show that in skeletal muscle cells and cardiomyocytes, the glucose transporter GLUT4 is a negative regulator of RIG-I-like receptor signaling during viral infection by redistributing RIG-I and MDA5 to the plasma membrane and attenuating interferon responses.

O’Shea and colleagues examine the three-dimensional chromatin architecture of the type 2 cytokine locus and how it differs between innate ILC2 cells and adaptive T_H2 lymphocytes.

Haniffa and colleagues provide diagnostic aids, potential biomarkers for disease staging and therapeutic strategies for cutaneous T cell lymphoma.

SLE is a heterogeneous disorder that is characterized by different immune endotypes. Faliti et al. follow the immune memory responses upon mRNA COVID-19 vaccinations in a large cohort of patients with SLE. They note that skewed immune responses, such as lower seroconversion and neutralization, might be due to extrafollicular B and T cell biases in SLE endotypes.

Here the authors show that high expression of MCT11 is key to the dysfunctionality associated with exhausted CD8⁺ T cells in tumors. By targeting MCT11, uptake of lactic acid, which is abundant in the tumor, is reduced, resulting in improved effector functions and tumor immunity.

Morley, Pomat and colleagues identify a homozygous mutation in COQ6 in an indigenous population of Papua New Guinea. This allele predisposes children to increased risk of acute lower respiratory infections in response to Streptococcus pneumoniae. This sensitivity is recapitulated in Coq6DY mice in the nonhematopoietic compartment.