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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.
Circulating immune stimuli access the joint through fenestrated capillaries that are located at the outer edge of the synovium. This area of vulnerability is policed by interacting macrophages and nociceptor neurons that work together as a functional unit.
In this Review, Sharma and colleagues describe the current landscape of combination therapies and discuss requirements for the development of effective combination strategies.
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.
In this Review, Herro and Grimes summarize the most recent key findings surrounding protective versus pathogenic functions of neutrophils, elaborating on phenotype-specific subsets of neutrophils and their involvement in homeostasis and disease.
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 TH2 lymphocytes.
Cutaneous T cell lymphoma is a rare, difficult to diagnose malignancy of T cells. Malignant T cells, together with populations of stromal cells and B cells, shape their own tumor niche for improved cancer cell survival in the skin.
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.
Woolf and colleagues review the current evidence that immune cells could promote pain resolution and prevention through direct effects on sensory neurons and through maintaining healthy tissue innervation.
Tumor-infiltrating T cells are known to encounter chronic antigens and hypoxia, which results in exhaustion and dysfunction. New data show that lactate fermentation, a characteristic of solid tumors, promotes the uptake of lactate into T cells via the monocarboxylate transporter MCT11, which reduces the metabolic fitness and anti-tumor function of these cells, an effect that might be targeted by immunotherapy.
