CAR-engineered lymphocyte persistence is governed by a FAS ligand/FAS auto-regulatory circuit.

Chimeric antigen receptor (CAR)-engineered T and NK cells can cause durable remission of B-cell malignancies; however, limited persistence restrains the full potential of these therapies in many patients. The FAS ligand (FAS-L)/FAS pathway governs naturally-occurring lymphocyte homeostasis, yet knowledge of which cells express FAS-L in patients and whether these sources compromise CAR persistence remains incomplete. Here, we constructed a single-cell atlas of diverse cancer types to identify cellular subsets expressing , the gene encoding FAS-L.

Blockade of LAG-3 in PD-L1-Deficient Mice Enhances Clearance of Blood Stage Malaria Independent of Humoral Responses.

T cells expressing high levels of inhibitory receptors such as PD-1 and LAG-3 are a hallmark of chronic infections and cancer. Checkpoint blockade therapies targeting these receptors have been largely validated as promising strategies to restore exhausted T cell functions and clearance of chronic infections and tumors. The inability to develop long-term natural immunity in malaria-infected patients has been proposed to be at least partially accounted for by sustained expression of high levels of inhibitory receptors on T and B lymphocytes.

Where Do Soldiers Really Come From? A Faculty Development Workshop on Veteran-Centered Care.

Problem: Addressing the medical concerns of veterans in both civilian health care systems and the Veterans Affairs (VA) health care system, where staff are familiar with issues of military reintegration, remains difficult but is increasingly important.

Approach: In 2013, the authors developed and implemented a faculty development workshop for practicing clinicians using the documentary Where Soldiers Come From. The workshop included topics on unconscious bias, the service member trajectory, health care disparities, and strategies for overcoming barriers to treating veterans with posttraumatic stress disorder and traumatic brain injury.

BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1.

During activation, T cells express receptors for receiving positive and negative costimulatory signals. Here we identify the B and T lymphocyte attenuator (BTLA), an immunoglobulin domain-containing glycoprotein with two immunoreceptor tyrosine-based inhibitory motifs. BTLA is not expressed by naive T cells, but it is induced during activation and remains expressed on T helper type 1 (T(H)1) but not T(H)2 cells.