Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Immune Checkpoint Blockade for the Treatment of Hodgkin Lymphoma.

ABSTRACT: Classical Hodgkin lymphoma is biologically different than other lymphomas. The cancer cells only occupy a small amount of the lymph node and evade the immune system by amplification of PD-L1 and PD-L2. Therefore, checkpoint inhibitors are a logical treatment option for Hodgkin lymphoma patients to unlock the immune system. Checkpoint inhibitors have shown high response rates in clinical trials in advanced-stage Hodgkin lymphoma. The two most commonly used checkpoint inhibitors are pembrolizumab and nivolumab, both FDA approved as third-line therapy. There is increasing interest in the use of checkpoint inhibitors with combination chemotherapy or with other targeted agents in the second-line or even frontline setting. In this review, we will highlight the clinical trials that led to approvals of checkpoint inhibitors for Hodgkin lymphoma.

SUBMITTER: Lin AY

PROVIDER: S-EPMC8882667 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Immune Checkpoint Blockade for the Treatment of Hodgkin Lymphoma.

Lin Adam Yuh AY Schnitter Joseph Michael JM Gordon Leo I LI

ImmunoTargets and therapy 20220223

Classical Hodgkin lymphoma is biologically different than other lymphomas. The cancer cells only occupy a small amount of the lymph node and evade the immune system by amplification of PD-L1 and PD-L2. Therefore, checkpoint inhibitors are a logical treatment option for Hodgkin lymphoma patients to unlock the immune system. Checkpoint inhibitors have shown high response rates in clinical trials in advanced-stage Hodgkin lymphoma. The two most commonly used checkpoint inhibitors are pembrolizumab ...[more]

PMID: 35237537

Similar Datasets

Impact of Treatment Beyond Progression with Immune Checkpoint Blockade in Hodgkin Lymphoma.

Project description:Atypical response patterns following immune checkpoint blockade (ICB) in Hodgkin lymphoma (HL) led to the concept of continuation of treatment beyond progression (TBP); however, the longitudinal benefit of this approach is unclear. We therefore performed a retrospective analysis of 64 patients treated with ICB; 20 who received TBP (TBP cohort) and 44 who stopped ICB at initial progression (non-TBP cohort). The TBP cohort received ICB for a median of 4.7 months after initial progression and delayed subsequent treatment by a median of 6.6 months. Despite receiving more prior lines of therapy, the TBP cohort achieved longer progression-free survival with post-ICB treatment (median, 17.5 months vs. 6.1 months, p = .035) and longer time-to-subsequent treatment failure, defined as time from initial ICB progression to failure of subsequent treatment (median, 34.6 months vs. 9.9 months, p = .003). With the limitations of a retrospective study, these results support the clinical benefit of TBP with ICB for selected patients.

| S-EPMC7288660 | biostudies-literature

Checkpoint blockade in Hodgkin and non-Hodgkin lymphoma.

Project description:Classical Hodgkin lymphoma (cHL) is characterized by nearly universal genetic alterations in 9p24.1, resulting in constitutive expression of PD-1 ligands. This likely underlies the unique sensitivity of cHL to PD-1 blockade, with response rates of ∼70% in relapsed/refractory disease. There are now numerous clinical trials testing PD-1 inhibitors in earlier stages of treatment and in combination with many other therapies. In general, non-Hodgkin lymphomas (NHLs) do not display a high frequency of 9p24.1 alterations and do not share cHL's vulnerability to PD-1 blockade. However, a few entities have genetic or immunologic features that may predict sensitivity to immune checkpoint blockade. These include primary mediastinal B cell lymphoma, primary central nervous system lymphoma, and primary testicular lymphoma, which harbor frequent alterations in 9p24.1, as well as Epstein Barr virus (EBV)-infected lymphomas, where EBV infection leads to increased PD-L1 expression. Although these subtypes may be specifically vulnerable to PD-1 blockade, the majority of NHLs appear to be minimally sensitive to PD-1 blockade monotherapy. Current investigations in NHL are therefore focusing on targeting other checkpoints or studying PD-1-based combination therapy. Looking forward, additional insight into the most common mechanisms of resistance to immune checkpoint inhibitors will be important to guide rational clinical trial design. In this review, we describe the biological basis for checkpoint blockade in cHL and NHL and summarize the clinical data generated to date. Guided by our rapidly evolving understanding of the pathobiology of various lymphoma subtypes, we are hopeful that the role of checkpoint inhibitors in lymphoma treatment will continue to grow.

| S-EPMC5728646 | biostudies-literature

Immune Checkpoint Inhibition in Hodgkin Lymphoma.

Project description:Intricate systems of checkpoints such as the programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) axis regulate adaptive immune responses to protect against tissue damage. However, diverse cancers can exploit these pathways to evade or suppress antitumor immunity, leading to tumor progression. Correspondingly, immune checkpoint inhibitors that block PD-1/PD-L1 signaling have shown marked therapeutic efficacy in certain cancers, such as Hodgkin lymphoma. Reed-Sternberg cells, the hallmark cells of Hodgkin lymphoma, commonly overexpress PD-1 ligands, and recent clinical trials have demonstrated impressive response rates with the PD-1 inhibitors nivolumab and pembrolizumab in relapsed or refractory Hodgkin lymphoma, leading to their FDA approval in this setting. Current efforts are underway to improve clinical responses by incorporating PD-1 inhibitors into earlier treatment regimens and identifying therapeutic agents that synergize with PD-1 inhibitors. This review summarizes our understanding of the PD-1/PD-L1 axis in Hodgkin lymphoma, recent clinical studies of anti-PD-1 monotherapy and promising combination immunotherapy in the pipeline.

| S-EPMC6745954 | biostudies-literature

Immune-Checkpoint Blockade Therapy in Lymphoma.

Project description:Tumor cells use immune-checkpoint pathways to evade the host immune system and suppress immune cell function. These cells express programmed cell-death protein 1 ligand 1 (PD-L1)/PD-L2, which bind to the programmed cell-death protein 1 (PD-1) present on cytotoxic T cells, trigger inhibitory signaling, and reduce cytotoxicity and T-cell exhaustion. Immune-checkpoint blockade can inhibit this signal and may serve as an effective therapeutic strategy in patients with solid tumors. Several trials have been conducted on immune-checkpoint inhibitor therapy in patients with malignant lymphoma and their efficacy has been reported. For example, in Hodgkin lymphoma, immune-checkpoint blockade has resulted in response rates of 65% to 75%. However, in non-Hodgkin lymphoma, the response rate to immune-checkpoint blockade was lower. In this review, we evaluate the biology of immune-checkpoint inhibition and the current data on its efficacy in malignant lymphoma, and identify the cases in which the treatment was more effective.

| S-EPMC7432396 | biostudies-literature

JAK inhibition enhances checkpoint blockade immunotherapy in patients with Hodgkin lymphoma.

Project description:Unleashing antitumor T cell activity by checkpoint inhibitor immunotherapy is effective in cancer patients, but clinical responses are limited. Cytokine signaling through the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway correlates with checkpoint immunotherapy resistance. We report a phase I clinical trial of the JAK inhibitor ruxolitinib with anti-PD-1 antibody nivolumab in Hodgkin lymphoma patients relapsed or refractory following checkpoint inhibitor immunotherapy. The combination yielded a best overall response rate of 53% (10/19). Ruxolitinib significantly reduced neutrophil-to-lymphocyte ratios and percentages of myeloid suppressor cells but increased numbers of cytokine-producing T cells. Ruxolitinib rescued the function of exhausted T cells and enhanced the efficacy of immune checkpoint blockade in preclinical solid tumor and lymphoma models. This synergy was characterized by a switch from suppressive to immunostimulatory myeloid cells, which enhanced T cell division.

| S-EPMC11283877 | biostudies-literature

The Role of Immune Checkpoint Inhibitors in Classical Hodgkin Lymphoma.

Project description:Hodgkin Lymphoma (HL) is a unique disease entity both in its pathology and the young patient population that it primarily affects. Although cure rates are high, survivorship can be linked with significant recent long-term morbidity associated with both chemotherapy and radiotherapy. The most significant advances have been with the use of the anti-CD30-drug conjugated antibody brentuximab vedotin (BV) and inhibitors of program death 1 (PD-1). HL is genetically wired to up-regulate program death ligand 1 (PD-L1) in >95% of cases, creating a state of so-called “T cell exhaustion”, which can be reversed with immune checkpoint-inhibitor blockade. The overall and complete response rates to PD-1 inhibitors in patients with relapsed or refractory HL are 70% and 20%, respectively, with a long median duration of response of ~16 months. In fact, PD-1 inhibitors can benefit a wide spectrum of relapsed HL patients, including some who have “progressive disease” by strict response criteria. We review the biology of HL, with a focus on the immune micro-environment and mechanisms of immune evasion. We also provide the rationale supporting the use of PD-1 inhibitors in HL and highlight some of the challenges of monitoring disease response in patients treated with this immunotherapy.

| S-EPMC6025119 | biostudies-literature

Immune checkpoint blockade therapy for bladder cancer treatment.

Project description:Bladder cancer remains the most immunogenic and expensive malignant tumor in the United States today. As the 4th leading cause of death from cancer in United States, Immunotherapy blocking immune checkpoints have been recently been applied to many aggressive cancers and changed interventions of urological cancers including advanced bladder cancer. The applied inhibition of PD-1-PD-L1 interactions can restore antitumor T-cell activity and enhance the cellular immune attack on antigens. The overall goals of this short review article are to introduce current cancer immunotherapy and immune checkpoint inhibitors, and to provide new insight into the underlying mechanisms that block immune checkpoints in tumor microenvironment. Furthermore, this review will address the preclinical and clinical trials to determine whether bladder cancer patients could benefit from this new cancer therapy in near future.

| S-EPMC4910761 | biostudies-literature

Immune Checkpoint Inhibition in Classical Hodgkin Lymphoma: From Early Achievements towards New Perspectives.

Project description:Immune checkpoint inhibition (ICI) became one of the major breakthroughs in cancer treatment over the past decade and entered into therapy within standard oncohematology practice. ICI has demonstrated impressive response rates as salvage therapy in relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) and is now being tested as an adjunction to chemotherapy in the frontline settings. CHL exquisite sensitivity to PD-1/PD-L1 axis inhibition relies on a particular biological background. By contrast, non-Hodgkin lymphomas (NHL) have demonstrated heterogeneous response rates using ICI. These observations highlight discrepancies between various types of lymphomas in terms of genetic alterations, immune microenvironment interactions, and disease phenotype. This review aims to focus on cHL immune escape mechanisms, focusing on cHL biological sensitivity to PD-1 blockade. We will summarize the available data issued from clinical trials on ICI in cHL and its safety profile. Going beyond the current use of monoclonal antibodies (mAb) targeting immune checkpoints in clinical practice, we will offer an overview of new combinatory therapeutic perspectives where cHL immunotherapy may be considered.

| S-EPMC6530161 | biostudies-literature

Checkpoint CD47 expression in classical Hodgkin lymphoma.

Project description:The glycoprotein CD47 regulates antiphagocytic activity via signal regulatory protein alpha (SIRPa). This study investigated CD47 expression on Hodgkin and Reed-Sternberg (HRS) cells in the classical Hodgkin lymphoma (cHL) tumour microenvironment and its correlation with prognosis, programmed-death (PD) immune markers, and SIRPa+ leukocytes. We conducted immunohistochemistry with CD47 and SIRPa antibodies on diagnostic biopsies (tissue microarrays) from cHL patients from two cohorts (n = 178). In cohort I (n = 136) patients with high expression of CD47 on HRS cells (n = 48) had a significantly inferior event-free survival [hazard ratio (HR) = 5.57; 95% confidence interval (CI), 2.78-11.20; p < 0.001] and overall survival (OS) (HR = 8.54; 95% CI, 3.19-22.90; p < 0.001) compared with patients with low expression (n = 88). The survival results remained statistically significant in multivariable Cox regression adjusted for known prognostic factors. In cohort II (n = 42) high HRS cell CD47 expression also carried shorter event-free survival (EFS) (HR = 5.96; 95% CI, 1.20-29.59; p = 0.029) and OS (HR = 5.61; 95% CI, 0.58-54.15; p = 0.136), although it did not retain statistical significance in the multivariable analysis. Further, high CD47 expression did not correlate with SIRPa+ leukocytes or PD-1, PD-L1 and PD-L2 expression. This study provides a deeper understanding of the role of CD47 in cHL during an era of emerging CD47 therapies.

| S-EPMC9310712 | biostudies-literature

Treatment Progress of Immune Checkpoint Blockade Therapy for Glioblastoma.

Project description:Glioblastoma (GBM) is a highly malignant and aggressive primary brain tumor mostly prevalent in adults and is associated with a very poor prognosis. Moreover, only a few effective treatment regimens are available due to their rapid invasion of the brain parenchyma and resistance to conventional therapy. However, the fast development of cancer immunotherapy and the remarkable survival benefit from immunotherapy in several extracranial tumor types have recently paved the way for numerous interventional studies involving GBM patients. The recent success of checkpoint blockade therapy, targeting immunoinhibitory proteins such as programmed cell death protein-1 and/or cytotoxic T lymphocyte-associated antigen-4, has initiated a paradigm shift in clinical and preclinical investigations, and the use of immunotherapy for solid tumors, which would be a potential breakthrough in the field of drug therapy for the GBM treatment. However clinical trial showed limited benefits for GBM patients. The main reason is drug resistance. This review summarizes the clinical research progress of immune checkpoint molecules and inhibitors, introduces the current research status of immune checkpoint inhibitors in the field of GBM, analyzes the molecular resistance mechanism of checkpoint blockade therapy, proposes corresponding re-sensitive strategies, and describes a reference for the design and development of subsequent clinical studies on immunotherapy for GBM.

| S-EPMC7734213 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data