Background As single agents, durvalumab (MEDI4736), a human IgG1 anti-PD-L1 antibody, and tremelimumab, a human IgG2 anti-CTLA-4 antibody, have shown acceptable safety profiles and antitumor activity. Similar to other anti-PD-L1/anti-PD-1 monotherapies, durvalumab has shown greater objective tumor response rates in PD-L1positive patients compared with PD-L1-negative patients. Anti-CTLA4 therapi...

Background Anti-PD1/PD-L1 monoclonal antibodies (mAbs) increase overall survival compared to standard of care (SOC) in different tumors. However, a proportion of patients (pts) will have progressive disease (PD) as best response. We conducted a meta-analysis to study the rates of response comparing these antibodies with SOC. Methods A search of published trials in MEDLINE and EMBASE analyzing...

Safety of a rechallenge with an immune checkpoint inhibitor (ICI) after immune-related adverse event (irAE) remains unclear, especially for those patients ICI class switch. All drug reactions involving at least one reported up to December 31, 2021 were extracted from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. The primary outcome was recurrence initial i...

PD-1 and its ligands PD-L1 PD-L2 are widely expressed on the surface of a variety cells group costimulatory molecules related to negative immune regulation. The activation PD-1/PD-L1 signaling pathway is beneficial for tumors escape from surveillance, but specific tumor mechanism not yet clear. As far as efficacy anti-PD-1 anti-PD-L1 antibodies concerned, more in-depth research mechanisms still...

The combination of targeted therapy with BRAF and MEK inhibitors has become the standard of care in patients with BRAF (V600E) mutant melanoma, but responses are not durable. In addition, the impressive clinical benefits with anti-PD-1 and anti-PD-L1 antibodies (Ab) in patients with heavily pretreated metastatic melanoma and the synergistic effect of dabrafenib, trametinib and anti-PD-1 compare...

Concurrent blockade of LAG-3 may enhance efficacy anti-programmed cell death-1 (PD-1) therapies. We present updated safety and clinical activity data from patients (pts) with advanced mel treated concurrent anti-LAG-3 (fianlimab) anti-PD-1 (cemiplimab). This Phase 1 study included pts unresectable or metastatic (excluding uveal mel) who were anti–PD-ligand (L)1 treatment naïve (expansion cohort...

OBJECTIVE This study was designed to investigate the roles of programmed death-1 (PD-1) and PD-1 ligands (PD-L) in the development of murine acute myocarditis caused by Coxsackievirus B3. PD-1/PD-L belong to the CD28/B7 superfamily, and the PD-1/PD-L pathway is known to transduce a negative immunoregulatory signal that antagonizes the T-cell receptor-CD28 signal and inhibits T-cell activation. ...

The dysregulation of immune checkpoints by tumors is an important mechanism of immune resistance, as administration of checkpoint inhibitors has resulted in impressive clinical responses in patients with late stage cancers. However, a subset of patients exhibits insufficient or no clinical response presumably due to the absence of tumor-specific cytotoxic T lymphocytes (CTLs). This supports the...

INTRODUCTION A major pathophysiologic mechanism in sepsis is impaired host immunity which results in failure to eradicate invading pathogens and increased susceptibility to secondary infections. Although many immunosuppressive mechanisms exist, increased expression of the inhibitory receptor programmed cell death 1 (PD-1) and its ligand (PD-L1) are thought to play key roles. The newly recognize...

PD-1/PD-L1 immunotherapy is viewed as having clinical benefits in advanced cancers but is effective in only a few patients, suggesting that an efficient combination approach is needed to improve efficacy. Immunohistochemistry analysis indicated that PD-L1 expression was correlated with the E6 expression in tumors from 122 lung cancer patients. The poorest survival occurred in PD-L1-positive/E6-...