Objective: To summarize and compare the therapeutic efficacy of programmed death 1 (PD-1) and cytotoxic T lymphocyte associated antigen 4 (CTLA-4) pathway inhibitors in the treatment of non-small-cell lung cancer (NSCLC). Methods: Traditional and network meta-analysis of clinical phase II/III randomized controlled trials of PD-1 and CTLA-4 pathway inhibitors vs. controls (general chemotherapy o...

Genetic polymorphisms in the human genome are an important component of genotypic variability including one's immune status. Single nucleotide polymorphisms (SNPs) in the cytotoxic T-lymphocyte antigen 4 (CTLA-4) gene have been linked to susceptibility to autoimmune disease. Interestingly, we have recently shown that an SNP in the CTLA-4 coding region (49A > G) is also associated with susceptib...

Viral persistence is associated with hierarchical antiviral CD8 T cell exhaustion with increased programmed death-1 (PD-1) expression. In HCV persistence, HCV-specific CD8 T cells from the liver (the site of viral replication) display increased PD-1 expression and a profound functional impairment that is not reversed by PD-1 blockade alone. Here, we report that the inhibitory receptor cytotoxic...

BACKGROUND Cytotoxic T lymphocyte associated antigen-4 (CTLA-4) is involved in the activation pathways of T lymphocytes. It has been shown that the circulating form of CTLA-4 is elevated in patients with hymenoptera allergy and can be down regulated by immunotherapy. OBJECTIVE to assess the effects on CTLA-4 of venom immunotherapy, given with different induction protocols: conventional (6 wee...

Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) functions as a negative regulator of endogenous and vaccine-induced antitumor immunity. The administration of fully human anti-CTLA-4 blocking monoclonal antibodies to advanced-cancer patients increases immune-mediated tumor destruction in some subjects. Nonetheless, patients that respond also frequently manifest serious inflammatory patholog...

PURPOSE Blockade of CTL-associated antigen-4 (CTLA-4), an inhibitory immunomodulatory molecule on T cells, has been shown to enhance T-cell responses and induce tumor rejection, and a number of clinical trials with anti-CTLA-4 blocking monoclonal antibody (mAb) are under way. However, accumulating evidence indicates that anti-CTLA-4 mAb increases the number of CD4+CD25+Foxp3+ regulatory T cells...

The survival rate of patients diagnosed with late-stage melanoma is poor--only 5%-10%. Enlisting the immune system in the fight against cancers such as melanoma could help improve the prognosis of these patients. Data have shown that melanocyte proteins make good targets for immune system-based therapy in this disease. However, self-tolerance, which develops to inhibit autoimmune attack, makes ...

BACKGROUND Immune checkpoint inhibitors are effective cancer treatments, but molecular determinants of clinical benefit are unknown. Ipilimumab and tremelimumab are antibodies against cytotoxic T-lymphocyte antigen 4 (CTLA-4). Anti-CTLA-4 treatment prolongs overall survival in patients with melanoma. CTLA-4 blockade activates T cells and enables them to destroy tumor cells. METHODS We obtaine...

The potency of cancer immunotherapy can be enhanced by administration of high-avidity ligands specific to receptors expressed on T cells. Antibodies or cytokines are the main agents used in such capacity. Antibody-mediated inhibition of cytotoxic T cell antigen-4 (CTLA-4) function in mice augments antitumor immunity and could serve as an important adjunct in cancer immunotherapy. However, antib...

Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) is an immunoregulatory molecule expressed by activated T cells and resting CD4+CD25 T cells. In patients with advanced melanoma, anti-CTLA-4 antibody therapy achieves cancer regression in 15% of patients. Treatment may be associated with grade III/IV autoimmune manifestations that included dermatitis, enterocolitis, hepatitis, uveitis, and ra...