The type 2 cytokine Fc-IL-4 revitalizes exhausted CD8 T cells against cancer.

Current cancer immunotherapy predominately focuses on eliciting type 1 immune responses fighting cancer; however, long-term complete remission remains uncommon. A pivotal question arises as to whether type 2 immunity can be orchestrated alongside type 1-centric immunotherapy to achieve enduring response against cancer. Here we show that an interleukin-4 fusion protein (Fc-IL-4), a typical type 2 cytokine, directly acts on CD8 T cells and enriches functional terminally exhausted CD8 T (CD8 T) cells in the tumour.

PPARβ/δ-orchestrated metabolic reprogramming supports the formation and maintenance of memory CD8 T cells.

The formation of memory T cells is a fundamental feature of adaptative immunity, allowing the establishment of long-term protection against pathogens. Although emerging evidence suggests that metabolic reprogramming is crucial for memory T cell differentiation and survival, the underlying mechanisms that drive metabolic rewiring in memory T cells remain unclear. Here, we found that up-regulation of the nuclear receptor peroxisome proliferator-activated receptor β/δ (PPARβ/δ) instructs the metabolic reprogramming that occurs during the establishment of central memory CD8 T cells.

Investigation of a fluorescent reporter microenvironment niche labeling strategy in experimental brain metastasis.

Brain metastases are the most common brain tumors in patients and are associated with poor prognosis. Investigating the colonization and outgrowth of brain metastases is challenging given the complexity of the organ, tissue sampling difficulty, and limited experimental models. To address this challenge, we employed a strategy to analyze the metastatic niche in established lesions, based on the release of a cell-penetrating mCherry tag from labeled tumor cells to neighboring niche cells, using different brain metastasis mouse models.

Emergence and fate of stem cell-like CD8 T cells during a primary immune response to viral infection.

In response to infection, naïve CD8 T (T) cells yield a large pool of short-lived terminal effector (T) cells that eliminate infected host cells. In parallel, a minor population of stem cell-like central memory (T) cells forms, which has the capacity to maintain immunity after pathogen clearance. It has remained uncertain whether stem-like T cells arise by dedifferentiation from a subset of cytolytic T cells or whether priming generates stem-like cells capable of seeding the T compartment and, if so, when cytolytic T cells branch off.

Activation of the transcription factor NFAT5 in the tumor microenvironment enforces CD8 T cell exhaustion.

Persistent exposure to antigen during chronic infection or cancer renders T cells dysfunctional. The molecular mechanisms regulating this state of exhaustion are thought to be common in infection and cancer, despite obvious differences in their microenvironments. Here we found that NFAT5, an NFAT family transcription factor that lacks an AP-1 docking site, was highly expressed in exhausted CD8 T cells in the context of chronic infections and tumors but was selectively required in tumor-induced CD8 T cell exhaustion.