Cell-Intrinsic CD38 Expression Sustains Exhausted CD8 T Cells by Regulating Their Survival and Metabolism during Chronic Viral Infection.

Acute and chronic viral infections result in the differentiation of effector and exhausted T cells with functional and phenotypic differences that dictate whether the infection is cleared or progresses to chronicity. High CD38 expression has been observed on CD8 T cells across various viral infections and tumors in patients, suggesting an important regulatory function for CD38 on responding T cells. Here, we show that CD38 expression was increased and sustained on exhausted CD8 T cells following chronic lymphocytic choriomeningitis virus (LCMV) infection, with lower levels observed on T cells from acute LCMV infection.

Marine vampires: Persistent, internal associations between bacteria and blood-feeding marine annelids and crustaceans.

Persistent bacterial presence is believed to play an important role in host adaptation to specific niches that would otherwise be unavailable, including the exclusive consumption of blood by invertebrate parasites. Nearly all blood-feeding animals examined so far host internal bacterial symbionts that aid in some essential aspect of their nutrition. Obligate blood-feeding (OBF) invertebrates exist in the oceans, yet symbiotic associations between them and beneficial bacteria have not yet been explored.

PD-1 Immune Checkpoint Blockade and PSGL-1 Inhibition Synergize to Reinvigorate Exhausted T Cells.

Chronic viral infections where the antigen persists long-term, induces an exhaustion phenotype in responding T cells. It is now evident that immune checkpoints on T cells including PD-1, CTLA-4, and PSGL-1 () are linked with the differentiation of exhausted cells. Chronic T cell receptor signaling induces transcriptional signatures that result in the development of various exhausted T cell subsets, including the stem-like T cell precursor exhausted (Tpex) cells, which can be reinvigorated by immune checkpoint inhibitors (ICIs).

The cure from within? a review of the microbiome and diet in melanoma.

Therapy for cutaneous melanoma, the deadliest of the skin cancers, is inextricably linked to the immune system. Once thought impossible, cures for metastatic melanoma with immune checkpoint inhibitors have been developed within the last decade and now occur regularly in the clinic. Unfortunately, half of tumors do not respond to checkpoint inhibitors and efforts to further exploit the immune system are needed.

Targeting the PSGL-1 Immune Checkpoint Promotes Immunity to PD-1-Resistant Melanoma.

Immune-checkpoint inhibitors have had impressive efficacy in some patients with cancer, reinvigorating long-term durable immune responses against tumors. Despite the clinical success of these therapies, most patients with cancer continue to be unresponsive to these treatments, highlighting the need for novel therapeutic options. Although P-selectin glycoprotein ligand-1 (PSGL-1) has been shown to inhibit immune responses in a variety of disease models, previous work has yet to address whether PSGL-1 can be targeted therapeutically to promote antitumor immunity.

Programmable siRNA pro-drugs that activate RNAi activity in response to specific cellular RNA biomarkers.

Since Paul Ehrlich's introduction of the "magic bullet" concept in 1908, drug developers have been seeking new ways to target drug activity to diseased cells while limiting effects on normal tissues. In recent years, it has been proposed that coupling riboswitches capable of detecting RNA biomarkers to small interfering RNAs (siRNAs) to create siRNA pro-drugs could selectively activate RNA interference (RNAi) activity in specific cells. However, this concept has not been achieved previously.

PSGL-1 Immune Checkpoint Inhibition for CD4 T Cell Cancer Immunotherapy.

Immune checkpoint inhibition targeting T cells has shown tremendous promise in the treatment of many cancer types and are now standard therapies for patients. While standard therapies have focused on PD-1 and CTLA-4 blockade, additional immune checkpoints have shown promise in promoting anti-tumor immunity. PSGL-1, primarily known for its role in cellular migration, has also been shown to function as a negative regulator of CD4 T cells in numerous disease settings including cancer.