PD-1 Articles

Bladder cancer is the sixth most common cancer in the US and most tumors have urothelial (transitional cell) histology. Platinum-based chemotherapy has long been the standard of care in advanced disease, but long-term outcomes have largely remained poor.

To clarify comprehensive immunological signature patterns of tumour tissue-infiltrating lymphocytes in patients with renal cell carcinoma and show its clinical significance.

We investigated the surface marker expressions of tumour tissue-infiltrating lymphocytes quantitatively and classified them based on their functional populations.

Intravesical Bacillus Calmette-Guerin (BCG) is an effective immunotherapy for non-muscle invasive bladder cancer (NMIBC). However, recurrence and progression remain frequent warranting deeper insights into its mechanism.

Immunotherapy for the treatment of cancer has made significant progresses over the last 20 years. Multiple efforts have been attempted to restore immune-mediated tumor elimination, leading to the development of several targeted immunotherapies.

Until recently, effective treatment options for patients with advanced urothelial carcinoma were limited to platinum-based chemotherapy. In the post-platinum setting and for patients ineligible for cisplatin, minimally effective second-line chemotherapy was used and outcomes were poor.

Treatment of cancer patients involves a multidisciplinary approach including surgery, radiotherapy, and chemotherapy. Traditionally, patients with metastatic disease are treated with combination chemotherapies or targeted agents.

Prostate cancer (PCa) is the most common malignancy in men and the cause for the second most common cancer-related death in the western world. Despite ongoing development of novel approaches such as second generation androgen receptor targeted therapies, metastatic disease is still fatal.

Immunotherapy is rapidly transforming cancer care across a range of tumor types. Although Sipuleucel-T represented the first successful vaccine for the treatment of established cancer, other immunotherapeutic approaches for prostate cancer such as checkpoint inhibitors have been relatively disappointing to date.

Advances in understanding the mechanisms of tumour-induced immunosuppression have led to the development of immune-checkpoint inhibitors in cancer patients, including those with renal cell carcinoma (RCC).

Renal cell carcinoma (RCC) is a highly immunogenic neoplasm, and cytokine-based immunotherapies have been used for decades with limited success. In recent years, antibody-based immunotherapies targeting immune checkpoint receptors PD-1 and CTLA-4 have demonstrated clinical efficacy in metastatic RCC (mRCC) patients, leading to regulatory approval of the combination of nivolumab and ipilimumab in treatment-naïve patients with intermediate- or poor-risk disease in April 2018.

Checkpoint receptor blockers, known to act by blocking the pathways that inhibit immune cell activation and stimulate immune responses against tumor cells, have been immensely successful in the treatment of cancer.

Long-term responders (LTRs) are defined by at least 18 months of response to sunitinib in metastatic clear-cell renal cell carcinoma (ccRCC). Well-described by clinical studies, the phenotype of these tumors has never been explored.

The activity of PD-1/PD-L1 inhibitors in the treatment of advanced bladder cancer (BC) is promising for many patients. However, a subset of patients do not benefit from treatment, thus leading to an effort to better identify predictive molecular biomarkers of response.

Despite the high sensitivity of renal cell carcinoma (RCC) to immunotherapy, RCC has been recognized as an unusual disease in which CD8+ T-cell infiltration into the tumor beds is related to a poor prognosis.

The advent of immunotherapy has heralded a number of significant advances in the treatment of particular malignancies associated with poor prognosis (melanoma, non-small-cell lung, renal and head/neck cancers).

Introduction: Metastatic renal cell carcinoma (mRCC) in recent years has been one of the diseases in the oncology that has experienced the greatest development of targeted therapies.Area covered: On one hand, more and more refined acquisitions of molecular biology are allowing a better sub-classification of this tumor, identifying new and peculiar biological profiles of patients with metastatic renal cancer that will soon be destined for increasingly tailored treatments.

To characterize the outcomes of patients with nonmelanoma solid tumors receiving anti-PD-1 immunotherapy not funded by the Australian Pharmaceutical Benefits Scheme.

Medical records of patients with metastatic nonmelanoma tumor diagnoses treated with anti-PD-1 (self-funded pembrolizumab or nivolumab through an access program) from January 1, 2014, to December 31, 2016, at Peter MacCallum Cancer Centre, were retrospectively reviewed.

To investigate the long-term follow-up outcomes of nivolumab monotherapy for previously treated metastatic renal cell carcinoma, using real-world data.

A total of 121 patients were treated with nivolumab monotherapy as subsequent therapy after the failure of prior tyrosine kinase inhibitor therapy between January 2013 and December 2021 at four affiliated institutions.

Immune checkpoint inhibitors are designed to restore a patient's own antitumor immune response, which has been suppressed during tumor development. The first monoclonal antibodies against the immune checkpoint programmed death 1 (PD-1) receptor, nivolumab and pembrolizumab, have now been approved for clinical use.

The pre-existing tumor-infiltrating T cell landscape in urothelial cell carcinoma of the bladder (UCB) may obtain prognostic significance and guide treatment decisions, particularly regarding immunotherapy.

In this study, we aimed to identify prognostic factors of cancer mortality in patients who received radical cystectomy and to identify genomic alterations in a sub-cohort of patients with locally advanced (pT3-4) and/or positive lymph nodes bladder cancer (BC).

Programmed cell death protein 1 (PD-1) and its ligands PD-L1 and PD-L2 play critical roles in maintaining an immunosuppressive tumor microenvironment. The purpose of the present study was to assess expression of PD-1, PD-L1, and PD-L2 in mouse prostate tumors.

Pharmacological inhibition of immune checkpoint receptors or their ligands represents a transformative breakthrough in the management of multiple cancers. However, immune checkpoint inhibitors have yet to be FDA-approved for the management of metastatic prostate cancer (PCa), the commonest non-cutaneous malignancy in men.

The programmed death receptor 1 (PD-1) protein is a cell-surface receptor on certain lymphocytes that, with its ligand programmed death ligand 1 (PD-L1), helps to down-regulate immune responses. Many cancer types express PD-L1 and evade immune recognition via the PD-1/PD-L1 interaction.

Persistent antigen exposure leads to the accumulation of lymphocytes and subsequent tertiary lymphoid structures (TLS). We investigated the relationship of tumor microenvironment (TME) with respect to programmed death ligand 1 (PD-L1), its receptor programmed death 1 (PD-1), and TLS in upper tract urothelial carcinoma (UTUC) cases and compared them with UTUC associated with urothelial bladder carcinoma (UTUC-BCa).

Immune checkpoint inhibitors (ICI) are extremely expensive and most patients with metastatic urothelial carcinoma (mUC) do not benefit significantly from their use.

We performed a systematic review and meta-analysis to determine response rates and survival outcomes on patients with mUC progressing despite prior platinum-based chemotherapy receiving ICI stratified by biomarker status.

The immune system is important to control tumor development and progression. However, tumor cells and cells of the tumor microenvironment can induce immune escape mechanisms including activation of immune checkpoints such as PD-1/PD-L1.

Immunotherapies have revolutionized the management of various malignancies but have only recently been evaluated systematically in prostate cancer. Pembrolizumab, a programmed-death 1 (PD-1) blocking antibody, has been utilized in the small subset of prostate cancer patients with mismatch repair deficiency/microsatellite instability, but has now been assessed in broader populations of metastatic prostate cancer patients.

Recently, the Food and Drug Administration (FDA)/European Medicines Agency (EMA) restricted first-line use of atezolizumab and pembrolizumab in patients with metastasised urothelial carcinoma by defining distinct programmed cell death ligand-1 cut-offs.

Programmed death-1 receptor (PD-1) and programmed death-1 receptor-ligand (PD-L1) have been suggested to play a role as prognostic markers in clear cell renal cell carcinoma (ccRCC). The association between PD-L1 and prognosis seems to be more robust than for PD-1.

In renal cell carcinoma (RCC), several prognostic biomarkers have been identified and are under investigation. Several reports have shown that the expression of programmed death 1 (PD-1) and its ligand PD-L1 is associated with poor outcome for patients with RCC.

To evaluate the prognostic value of PD-L1 and PD-1 expression in upper tract urothelial carcinoma (UTUC) patients.

A retrospective multicenter study was conducted in 283 UTUC patients treated with radical nephroureterectomy (RNU) between 2000 and 2015 at 10 French hospitals.

Increasing availability of effective treatment options for metastatic renal cell carcinoma (mRCC) has highlighted the importance of identifying predictors of treatment response. Although PD-L1 expression in renal cancer has been reported as a predictor of treatment response and prognosis, its assessment by immunohistochemistry is invasive and difficult to perform repeatedly.

Clinical value and utility of checkpoint inhibitors, a drug class targeting adaptive immune suppression pathways (PD-1, PDL-1, and CTLA-4), is growing rapidly and maintains status of a landmark achievement in oncology.

Biomarkers predicting immunotherapy response in metastatic renal cell cancer (mRCC) are lacking. PD-L1 immunohistochemistry is a complementary diagnostic for immune checkpoint inhibitors (ICIs) in mRCC, but has shown minimal clinical utility and is not used in routine clinical practice.

Biomarkers that facilitate the prediction of disease recurrence in prostate cancer (PCa) may enable physicians to personalize treatment for individual patients. In the current study, PD-1 (PDCD1) promoter methylation was assessed in a cohort of 498 PCa patients included in The Cancer Genome Atlas (TCGA) and a second cohort of 300 PCa cases treated at the University Hospital of Bonn.

Immunotherapies targeting the PD-1 checkpoint pathway have recently gained regulatory approval in numerous cancer types. With the widespread use of immune checkpoint therapies, varying patterns of responses and immune-related adverse events are being observed.

Immunotherapy aimed at inhibiting the PD-1/PD-L1 immune checkpoint has been approved and used successfully for the treatment of bladder cancer. The identification of markers predictive of response to immune checkpoint inhibitors is critical to advancing the success of this therapy.

Checkpoint inhibitors target the inhibitory receptors expressed by tumor-infiltrating T cells in order to reinvigorate an anti-tumor immune response. Therefore, understanding T cell composition and phenotype in human tumors is crucial.

Checkpoint inhibitors (CPIs) are established as a standard therapy option for metastatic bladder cancer; however, their role in earlier-stage disease remains undefined.

To summarize the preclinical and clinical evidence forming the rationale for multiple ongoing investigations of CPIs in patients with localized bladder cancer defined by non-muscle-invasive or muscle-invasive stages.

Several tyrosine kinase inhibitors targeting the vascular endothelial growth factor receptors and molecules inhibiting the mammalian target of rapamycin are being used for management of metastatic renal cell carcinoma (mRCC); however, there is still a potential for improvement.

Systemic therapy for bladder cancer, both localized muscle-invasive disease and metastatic disease, has seen minimal progress over the past two decades. Current approaches rely upon cytotoxic chemotherapy combinations aimed at increasing cure rates or achieving palliation and disease control, but these regimens are fraught with short- and long-term toxicities and outcomes remain suboptimal.

Immunostimulatory therapies have been a cornerstone of treatment for metastatic renal cell carcinoma (RCC) since the 1990s. However, the use of traditional immunotherapeutic approaches for RCC, such as high-dose interleukin-2 and interferon-α, has been limited by significant systemic toxicities and the need to deliver these therapies at centers of expertise.

Immune checkpoint blockade (ICB) improved clinical outcomes in renal and bladder cancer patients, but the response rates remain limited especially in metastatic disease. While STAT3 transcription factor is well-known master regulator of tumor immune evasion, little is known about the role of STAT3 in the resistance of renal or bladder cancers to immunotherapy.

For the practicing clinician, the dilemma becomes how most appropriate to sequence the aforementioned regimens. It is challenging to be dogmatic, as there are no comparative studies juxtaposing novel front-line options directly-all of the available studies utilize a comparator arm of sunitinib.

To systematically evaluate the overall efficacy and safety of current anti-PD-1/PD-L1 antibodies for treatment of patients with advanced or refractory cancer.

Fifty-one trials including 6,800 patients were included.

Bladder cancer (BCa) shows its potential immunogenity in current immune-checkpoint inhibitor related immunotherapies. However, its therapeutic effects are improvable and could be affected by tumor immune microenvironment.

The programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) have shown positive efficacy in several solid cancers due to their targeted antitumour effects. However, the frequency and clinical implication value in prostate cancer still remain unclear.

Immune checkpoint inhibitor (ICI) therapy and therapeutic cancer vaccines have continued to demonstrate survival benefit and durable clinical response in patients with renal cell cancer, prostate cancer and bladder cancer, with limited responses in testicular cancer.

Immune biomarkers encompass a wide range of blood-borne and cell-associated molecules whose detection or expression may change in response to an immune therapy. These immune therapies encompass a range of platforms including autologous cellular products, in other words, dendritic cells, prime boost DNA vaccines, chimeric antigen receptor (CAR) T cells and checkpoint inhibitors.