PURPOSE To better understand the efficacy and safety of anti-PD-1/PD-L1 therapy (atezolizumab, pembrolizumab, nivolumab) in patients with previously treated advanced non-small-cell lung cancer (NSCLC). METHODS The Cochrane Controlled Trial Register, Embase, Medline, and the Science Citation Index were searched for prospective published reports of atezolizumab, pembrolizumab, nivolumab in prev...

Antibodies that block PD-L1/PD-1 immune checkpoints restore the activity of functionally-impaired antitumor T cells. These antibodies show unprecedented clinical benefit in various advanced cancers, particularly in melanoma. However, only a subset of cancer patients responds to current PD-L1/PD-1-blocking strategies, highlighting the need for further advancements in PD-L1/PD-1-based immunothera...

Exportin-1 (XPO1) is a nuclear export protein with >220 cargo proteins, including tumor suppressors and cell cycle modulators. Selinexor is a SINE (Selective Inhibitor of Nuclear Export) compound that has been administered to >900 cancer patients in Phase I and II trials to date, with evidence of efficacy and tolerability. Selinexor blocks nuclear export of NFAT1c, STAT1 and STAT3, which are im...

Immune checkpoint antibody-mediated blockade has gained attention as a new cancer immunotherapy strategy. Accumulating evidence suggests that this therapy imparts a survival benefit to metastatic melanoma and non-small cell lung cancer patients. A substantial amount of data on immune checkpoint antibodies has been collected from clinical trials; however, the direct effect of the antibodies on h...

Immunotherapies targeting the programmed death 1 (PD-1) coinhibitory receptor have shown great promise for a subset of patients with cancer. However, robust and safe combination therapies are still needed to bring the benefit of cancer immunotherapy to broader patient populations. To search for an optimal strategy of combinatorial immunotherapy, we have compared the antitumor activity of the an...

The programmed cell death ligand 1 (PD-L1) participates in an immune checkpoint system involved in preventing autoimmunity. PD-L1 is expressed on tumor cells, tumor-associated macrophages, and other cells in the tumor microenvironment. Anti-PD-L1 antibodies are active against a variety of cancers, and combined anti-PD-L1 therapy with external beam radiotherapy has been shown to increase therape...

Background Immunohistochemical detection of PD-L1 may be used in the future as a biomarker to help select an immunotherapeutic regimen for patients with advanced melanoma. For example, patients whose tumors are PD-L1+ may receive anti-PD-1 monotherapy, and those whose tumors are PD-L1(-) may receive combination anti-PD-1 and anti-CTLA-4. The evaluation of the utility of PD-L1 as a biomarker has...

BACKGROUND Immunotherapeutic approaches to treating cancer have been evaluated during the last few decades with limited success. An understanding of the checkpoint signaling pathway involving the programmed death 1 (PD-1) receptor and its ligands (PD-L1/2) has clarified the role of these approaches in tumor-induced immune suppression and has been a critical advancement in immunotherapeutic drug...

The PD-1/PD-L1 signaling pathway plays a crucial role in cancer immune evasion, and the use of anti-PD-1/PD-L1 antibodies represents significant milestone immunotherapy. However, low response rate observed unselected patients development therapeutic resistance remain major obstacles to their clinical application. Accumulating studies showed that overexpressed TGF-β is another immunosuppressive ...