Efficacy of CTLA-4 checkpoint therapy is dependent on IL-21 signaling to mediate cytotoxic reprogramming of PD-1CD8 T cells.

The mechanisms underlying the efficacy of anti-programmed cell death protein 1 (PD-1) and anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) therapy are incompletely understood. Here, by immune profiling responding PD-1CD8 T (T) cell populations from patients with advanced melanoma, we identified differential programming of T cells in response to combination therapy, from an exhausted toward a more cytotoxic effector program. This effect does not occur with anti-PD-1 monotherapy.

Combination anti-PD-1 and anti-CTLA-4 therapy generates waves of clonal responses that include progenitor-exhausted CD8 T cells.

Combination checkpoint blockade with anti-PD-1 and anti-CTLA-4 antibodies has shown promising efficacy in melanoma. However, the underlying mechanism in humans remains unclear. Here, we perform paired single-cell RNA and T cell receptor (TCR) sequencing across time in 36 patients with stage IV melanoma treated with anti-PD-1, anti-CTLA-4, or combination therapy.

SARS-CoV-2 inflammation durably imprints memory CD4 T cells.

Memory CD4 T cells are critical to human immunity, yet it is unclear whether viral inflammation during memory formation has long-term consequences. Here, we compared transcriptional and epigenetic landscapes of Spike (S)-specific memory CD4 T cells in 24 individuals whose first exposure to S was via SARS-CoV-2 infection or mRNA vaccination. Nearly 2 years after memory formation, S-specific CD4 T cells established by infection remained enriched for transcripts related to cytotoxicity and for interferon-stimulated genes, likely because of a chromatin accessibility landscape altered by inflammation.

Complete mitochondrial genome of the introduced Indian walking stick (Lonchodidae, Insecta) from California.

We present the complete mitochondrial genome of from Salinas, CA. The mitochondrial genome of is circular, AT rich (78.1%), and 16,671 bp in length.