Therapies that target cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) have provided unprecedented clinical benefits in various types of cancer.
Programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) is a negative immune checkpoint pathway that inhibit immune responses, and upregulation of this pathway has implications in many malignancies.
Blockade of immune checkpoint pathways by programmed cell death protein 1 (PD-1) antibodies has demonstrated broad clinical efficacy against a variety of malignancies.
Recently, it was discovered that the use of immunotherapeutic drugs targeting programmed cell death protein 1 (PD1)/programmed death ligand-1 (PD-L1) was associated with improved survival in several types of cancer (especially in patients with mismatch-repair (MMR) deficient patients).
Thus far, no recommendations for the use of PD-1 inhibitors to treat cancer in renal transplant patients are yet available, and very few cases reporting kidney-transplanted patients treated with PD-1 inhibitors are available in the literature.
PD-1 (CD279)-PD-L1 (CD274) inhibitory signaling is critical for cancer immune evasion, and thus has become one of the major targets in anticancer immunotherapy.
Among the 36 variables, estimated CD8+ T-cell abundance was the most predictive of the response to anti-PD-1/PD-L1 therapy across cancer types (Spearman R = 0.72; P < 2.3 × 10-4), followed by the tumor mutational burden (Spearman R = 0.68; P < 6.2 × 10-4), and the fraction of samples with high PD1 gene expression (Spearman R = 0.68; P < 6.9 × 10-4).
Immune checkpoint inhibitors, targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and the programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathways have shown remarkable potential in several types of cancer.
We reviewed 1444 patients treated with ICIs over 6 years at our cancer center, and from the 1163 patients who received programmed cell death protein 1 (PD-1) inhibitors, we identified 21 such cases, 12 of which developed new-onset insulin-dependent diabetes and 9 experienced worsening of pre-existing type 2 diabetes.
Head and neck cancers comprise the sixth most common cancer type in the United States with estimated 14,620 deaths in 2019.Two checkpoint inhibitors, e.g. antibodies against programmed cell death protein 1 (PD-1), are currently FDA approved for second-line therapy of recurrent and/or metastatic head and neck squamous cell carcinomas (HNSCC).
The findings revealed that <i>PD-1</i> rs2227981 and rs11568821 polymorphisms significantly decreased the overall cancer risk (Odds Ratio (OR) = 0.82, 95% CI = 0.68-0.99, <i>p</i> = 0.04, TT vs. CT+CC; OR = 0.79, 95% CI = 0.67-0.94, <i>p</i> = 0.006, AG vs. GG, and OR = 0.82, 95% CI = 0.70-0.96, <i>p</i> = 0.020, AG+AA vs. GG, respectively), while <i>PD-1</i> rs7421861 polymorphism significantly increased the risk of developing cancer (OR = 1.16, 95% CI = 1.02-1.33, <i>p</i> = 0.03, CT vs. TT).
Although immunotherapies that enhance immune responses by targeting programmed cell death-1(PD-1)/PD-L1 are being applied to malignancies, these treatments have shown limited response rates, suggesting that additional inhibitory receptors are also involved in T-cell exhaustion and tumor outcome.
Our study has implications for understanding the role of SATB1 in human health and disease and suggests an approach for modulating PD-1 in T cells, highly relevant to human malignancies or chronic viral infections.
Pembrolizumab, a monoclonal antibody against the programmed cell death 1 (PD-1) protein, can induce a stable regression of some malignancies refractory to conventional chemotherapy.
Checkpoint blockade antibodies targeting cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed cell death 1 (PD-1) and its ligands such as programmed cell death ligand 1 (PD-L1) have already revolutionized the treatment of multiple types of cancer and have significantly improved treatment and survival outcomes of patients affected by these malignancies.
Head and neck cancer is comprised of biologically distinct cancers, HPV-positive and HPV-negative, and the clinical responses to PD-1 inhibitors in both HPV-positive and HPV-negative head and neck patients have showcased better than any other cancer type that there are distinct pathways to immunogenicity that may lend themselves to different therapeutic approaches.
Although immunotherapy has revolutionized the oncology field, largely attributed to the success of immune-checkpoint blockade, the durability and efficacy of anti-PD1 (programmed cell death protein 1) mAb vary across different malignancies.
Over the past few years immune checkpoint inhibitors (ICI) targeting cytotoxic lymphocyte antigen-4 (CTLA-4), programmed cell death protein 1 (PD-1), and programmed cell death ligand 1 (PD-L1) have changed treatment paradigms in many malignancies and are currently under investigation in HNSCC as well.
This prospective observational study (ClinicalTrials.gov: NCT02420600) evaluated whether CTCs, circulating cancer stem-like cells (cCSCs), and peripheral lymphocytes with/without Programmed cell death protein 1 (PD-1) expression were associated with prognosis among patients receiving palliative chemotherapy for initially unresectable, recurrent/metastatic head and neck squamous cell carcinoma (rmHNSCC).
Expression of programmed cell death ligand 1 (PD-L1) on tumor cells contributes to cancer immune evasion by interacting with programmed cell death 1 on immune cells.