Anti-PD-L1 and anti-CD73 combination therapy promotes T cell response to EGFR-mutated NSCLC.

Treatment with anti-PD-1 and anti-PD-L1 therapies has shown durable clinical benefit in non-small cell lung cancer (NSCLC). However, patients with NSCLC with epidermal growth factor receptor (EGFR) mutations do not respond as well to treatment as patients without an EGFR mutation. We show that EGFR-mutated NSCLC expressed higher levels of CD73 compared with EGFR WT tumors and that CD73 expression was regulated by EGFR signaling.

A New Pipeline to Predict and Confirm Tumor Neoantigens Predict Better Response to Immune Checkpoint Blockade.

Mutations that drive oncogenesis in cancer can generate neoantigens that may be recognized by the immune system. Identification of these neoantigens remains challenging due to the complexity of the MHC antigen and T-cell receptor interaction. Here, we describe the development of a systematic approach to efficiently identify and validate immunogenic neoantigens.

Adipose-derived stromal cells promote allograft tolerance induction.

Amputations and unsalvageable injuries with devastating tissue loss are common in the combat wounded. Reconstructive transplantation in the civilian setting using vascular composite allotransplants (VCAs) with multiple tissues (skin, muscle, nerve, bone) combined with long-term multidrug immunosuppression has been encouraging. However, skin rejection remains a critical complication.

Ectopic bone formation in severely combat-injured orthopedic patients -- a hematopoietic niche.

Combat-related heterotopic ossification (HO) has emerged as a common and problematic complication of modern wartime extremity injuries, contributing to substantial patient morbidity and loss of function. We have previously reported that HO-forming patients exhibit a more pronounced systemic and local inflammatory response very early in the wound healing process. Moreover, traumatized muscle-derived mesenchymal progenitor cells from these patients have a skewed differentiation potential toward bone.