Browse
Submit Data
Databases
API
Help

Dataset Information

31 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Optimizing the Treatment Schedule of Radiotherapy Combined With Anti-PD-1/PD-L1 Immunotherapy in Metastatic Cancers.

ABSTRACT: Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein-1 (PD-1), and programmed cell death ligand-1 (PD-L1) have been approved for a variety of malignant tumors and are widely used to treat patients with metastatic disease. However, the efficacy of PD-1 inhibitors is limited due to tumor heterogeneity, high tumor burden, and "cold" tumor microenvironment. Radiotherapy can improve the anti-tumor effects of PD-1/PD-L1 inhibitors in various ways. As a new radiotherapy method, stereotactic body radiotherapy (SBRT) or hypofractionated radiotherapy (HFRT) provides higher doses per fraction to the target lesions, thus achieving immune activation effects and overcoming tumor resistance to anti-PD-1/PD-L1 treatment, which significantly improves the local and distant control of tumors. However, for different metastatic situations, radiotherapy plays different roles in the combination therapy. In oligometastatic status, radiotherapy can be used as a local radical treatment aiming to eliminate cancers in cooperation with systemic PD-1 inhibitors. In other circumstances, like bulky metastasis or multiple metastatic tumors, radiotherapy can be used as adjuvant to systemic immunotherapy. This review focuses on the underlying mechanisms and optimization strategies for the combination of radiotherapy and anti-PD-1/PD-L1 therapy in metastatic disease.

SUBMITTER: Kong Y

PROVIDER: S-EPMC8042160 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Abscopal effect of stereotactic radiotherapy combined with anti-PD-1/PD-L1 immunotherapy: Mechanisms, clinical efficacy, and issues.

Project description: Not available

| S-EPMC7743005 | biostudies-literature

Roles of cancer-associated fibroblasts (CAFs) in anti- PD-1/PD-L1 immunotherapy for solid cancers.

Project description:In recent years, breakthroughs have been made in tumor immunotherapy. However, tumor immunotherapy, particularly anti-PD-1/PD-L1 immune checkpoint inhibitors, is effective in only a small percentage of patients in solid cancer. How to improve the efficiency of cancer immunotherapy is an urgent problem to be solved. As we all know, the state of the tumor microenvironment (TME) is an essential factor affecting the effectiveness of tumor immunotherapy, and the cancer-associated fibroblasts (CAFs) in TME have attracted much attention in recent years. As one of the main components of TME, CAFs interact with cancer cells and immune cells by secreting cytokines and vesicles, participating in ECM remodeling, and finally affecting the immune response process. With the in-depth study of CAFs heterogeneity, new strategies are provided for finding targets of combination immunotherapy and predicting immune efficacy. In this review, we focus on the role of CAFs in the solid cancer immune microenvironment, and then further elaborate on the potential mechanisms and pathways of CAFs influencing anti-PD-1/PD-L1 immunotherapy. In addition, we summarize the potential clinical application value of CAFs-related targets and markers in solid cancers.

| S-EPMC9912573 | biostudies-literature

PD-L1 immunohistochemistry for canine cancers and clinical benefit of anti-PD-L1 antibody in dogs with pulmonary metastatic oral malignant melanoma.

Project description:Immunotherapy targeting programmed cell death 1 (PD-1) and PD-ligand 1 (PD-L1) represents promising treatments for human cancers. Our previous studies demonstrated PD-L1 overexpression in some canine cancers, and suggested the therapeutic potential of a canine chimeric anti-PD-L1 monoclonal antibody (c4G12). However, such evidence is scarce, limiting the clinical application in dogs. In the present report, canine PD-L1 expression was assessed in various cancer types, using a new anti-PD-L1 mAb, 6C11-3A11, and the safety and efficacy of c4G12 were explored in 29 dogs with pulmonary metastatic oral malignant melanoma (OMM). PD-L1 expression was detected in most canine malignant cancers including OMM, and survival was significantly longer in the c4G12 treatment group (median 143 days) when compared to a historical control group (n = 15, median 54 days). In dogs with measurable disease (n = 13), one dog (7.7%) experienced a complete response. Treatment-related adverse events of any grade were observed in 15 dogs (51.7%). Here we show that PD-L1 is a promising target for cancer immunotherapy in dogs, and dogs could be a useful large animal model for human cancer research.

| S-EPMC7881100 | biostudies-literature

Safety of PD-1/PD-L1 Inhibitors Combined With Palliative Radiotherapy and Anti-Angiogenic Therapy in Advanced Hepatocellular Carcinoma.

Project description:BackgroundPrevious studies have explored cancer immunotherapy with radiotherapy or anti-angiogenic therapy, but no trials have reported a triple therapy approach. This study aimed to investigate safety and clinical outcome of PD-1/PD-L1 inhibitors combined with palliative radiotherapy and targeted angiogenesis therapy in hepatocellular carcinoma (HCC) of Barcelona Clinic Liver Cancer (BCLC) stage C.MethodsConsecutive patients (n=16) treated with PD-1/PD-L1 inhibitors combined with radiotherapy and anti-angiogenic therapy in a bi-institutional cohort between July 2017 and December 2020 were retrospectively included. Radiotherapy was conducted within 14 days of the first administration of immunotherapy. The primary endpoint was treatment-related adverse event (TRAE).ResultsThe median follow-up was 383 days. Fifteen patients (93.8%) experienced at least 1 TRAE. The most common TRAEs of any grade were rash (25%), diarrhea (25%), aspartate aminotransferase increase (18.8%), alanine transaminase increase (18.8%), decreased appetite (18.8%), and fatigue (18.8%). Grade 3/4 TRAEs occurred in 4 patients (25%) and finally led to treatment interruption. No patient death was attributed to treatment. No specific events were responsible for the addition of radiotherapy. Six patients showed partial response, 7 showed stable disease, and 2 showed progressive disease. The objective response rate and disease control rate were 40.0% (95% CI 16.3%-67.7%) and 86.7% (95% CI 59.5%-98.3%), respectively. Moreover, the median progression-free survival was 140 days. Patients had a median overall survival of 637 days, and the estimated rates of survival at 6 and 12 months were 92.3% and 75.5%, respectively.ConclusionPD-1/PD-L1 inhibitors combined with palliative radiotherapy and anti-angiogenic therapy appear to be safe, with no unexpected adverse events. Additional studies exploring the clinical benefit are warranted.

| S-EPMC8170410 | biostudies-literature

Comprehensive Evaluation of Anti-PD-1, Anti-PD-L1, Anti-CTLA-4 and Their Combined Immunotherapy in Clinical Trials: A Systematic Review and Meta-analysis.

Project description:Immunotherapy with immune checkpoint inhibitor (ICI) drugs is gradually becoming a hot topic in cancer treatment. To comprehensively evaluate the safety and efficacy of ICI drugs, we employed the Bayesian model and conducted a network meta-analysis in terms of progression-free survival (PFS), overall survival (OS) and severe adverse events (AEs). Our study found that treatment with ipilimumab was significantly worse than standard therapies in terms of PFS, whereas treatment with cemiplimab significantly improved PFS. The results also indicated that cemiplimab was the best choice for PFS. Treatment with nivolumab, pembrolizumab and nivolumab plus ipilimumab significantly improved OS compared to standard therapies. In terms of OS, cemiplimab was found to be the best choice, whereas avelumab was the worst. In terms of severe AEs, atezolizumab, avelumab, durvalumab, nivolumab, and pembrolizumab all significantly reduced the risk of grade 3 or higher AEs compared to standard therapy. The least likely to be associated with severe AEs were as follows: cemiplimab, avelumab, nivolumab, atezolizumab, and camrelizumab, with nivolumab plus ipilimumab to be the worst. Therefore, different ICI drug therapies may pose different risks in terms of PFS, OS and severe AEs. Our study may provide new insights and strategies for the clinical practice of ICI drugs.

| S-EPMC9174611 | biostudies-literature

Autophagy-amplifying nanoparticles evoke immunogenic cell death combined with anti-PD-1/PD-L1 for residual tumors immunotherapy after RFA.

Project description:Incomplete radiofrequency ablation (IRFA) triggers mild protective autophagy in residual tumor cells and results in an immunosuppressive microenvironment. This accelerates the recurrence of residual tumors and causes resistance to anti-PD-1/PDL1 therapy, which bringing a great clinical challenge in residual tumors immunotherapy. Mild autophagy activation can promote cancer cell survival while further amplification of autophagy contributes to immunogenic cell death (ICD). To this regard, we constructed active targeting zeolitic imidazolate framework-8 (ZIF-8) nanoparticles (NPs) loaded with STF62247 or both STF62247 and BMS202, namely STF62247@ZIF-8/PEG-FA (SZP) or STF62247-BMS202@ZIF-8/PEG-FA (SBZP) NPs. We found that SZP NPs inhibited proliferation and stimulated apoptosis of residual tumor cells exposed to sublethal heat stress in an autophagy-dependent manner. Further results discovered that SZP NPs could amplify autophagy in residual tumor cells and evoke their ICD, which dramatically boosted the maturation of dendritic cells (DCs). Through vaccination experiments, we found for the first time that vaccination with heat + SZP treatment could efficiently suppress the growth of new tumors and establish long-term immunological memory. Furthermore, SBZP NPs could remarkably promote the ICD of residual tumor cells, obviously activate the anti-tumor immune microenvironment, and significantly inhibit the growth of residual tumors. Thus, amplified autophagy coupled with anti-PD-1/PDL1 therapy is potentially a novel strategy for treating residual tumors after IRFA.

| S-EPMC10548684 | biostudies-literature

Anti-PD1 and anti-PD-L1 in the treatment of metastatic melanoma.

Project description:Programmed cell death receptor-1 (PD-1) and programmed cell death-1 ligand-1 (PD-L1) represent promising novel targets in immunotherapy. PD-1 is an inhibitory receptor involved in T-cell regulation that is expressed by activated T cells. Nivolumab and pembrolizumab are anti-PD-1 antibodies that have shown antitumor activity and acceptable tolerability in patients with metastatic melanoma in preclinical development and Phase I/II clinical trials. Several ongoing Phase III studies are further investigating the efficacy and safety of anti-PD-1 therapy in melanoma. Initial data on the combination of anti-PD-1 and anti-cytotoxic T-lymphocyte-associated antigen 4 blockade with nivolumab and ipilimumab also appear promising. Monoclonal antibodies to blockade PD-L1 may also be an effective immunotherapy strategy in melanoma and several anti-PD-L1 antibodies are in development.

| S-EPMC6094609 | biostudies-literature

CD47KO/CRT dual-bioengineered cell membrane-coated nanovaccine combined with anti-PD-L1 antibody for boosting tumor immunotherapy.

Project description:Tumor vaccines trigger tumor-specific immune responses to prevent or treat tumors by activating the hosts' immune systems, and therefore, these vaccines have potential clinical applications. However, the low immunogenicity of the tumor antigen itself and the low efficiency of the vaccine delivery system hinder the efficacy of tumor vaccines that cannot produce high-efficiency and long-lasting antitumor immune effects. Here, we constructed a nanovaccine by integrating CD47KO/CRT dual-bioengineered B16F10 cancer cell membranes and the unmethylated cytosine-phosphate-guanine (CpG) adjuvant. Hyperbranched PEI25k was used to load unmethylated cytosine-phosphate-guanine (CpG) through electrostatic adsorption to prepare PEI25k/CpG nanoparticles (PEI25k/CpG-NPs). CD47KO/CRT dual-bioengineered cells were obtained by CRISPR-Cas9 gene editing technology, followed by the cell surface translocation of calreticulin (CRT) to induce immunogenic cell death (ICD) in vitro. Finally, the extracted cell membranes were coextruded with PEI25k/CpG-NPs to construct the CD47KO/CRT dual-bioengineered cancer cell membrane-coated nanoparticles (DBE@CCNPs). DBE@CCNPs could promote endocytosis of antigens and adjuvants in murine bone marrow derived dendritic cells (BMDCs) and induce their maturation and antigen cross-presentation. To avoid immune checkpoint molecule-induced T cell dysfunction, the immune checkpoint inhibitor, the anti-PD-L1 antibody, was introduced to boost tumor immunotherapy through a combination with the DBE@CCNPs nanovaccine. This combination therapy strategy can significantly alleviate tumor growth and may open up a potential strategy for clinical tumor immunotherapy.

| S-EPMC9535270 | biostudies-literature

Hyperprogressive Disease After Combined Anti-PD-L1 and Anti-CTLA-4 Immunotherapy for MSI-H/dMMR Gastric Cancer: A Case Report.

Project description:Immune checkpoint inhibitors (ICI) have been developed in gastric adenocarcinomas and approved in first-line metastatic setting (in combination with chemotherapy) as well as in pretreated patients. Microsatellite instability-high (MSI-H) tumors are predicted to derive high benefit from ICI but data in gastric locations are limited. Here, we describe the case of a 68-year old patient with stage IV MSI-H gastric adenocarcinoma, referred to our center to receive immunotherapy after failure of standard of care (surgery with perioperative platin-based chemotherapy and paclitaxel plus ramucirumab at disease progression). The patient received one injection of durvalumab and tremelimumab and was hospitalized eighteen days after because of occlusive syndrome. The CT scan showed hyperprogression of the lymph nodes and hepatic lesions, compressing the gastric stump. He died few days later. Molecular analyses did not explain this outcome. To our knowledge, this is one of the first reported cases of hyperprogressive disease after combined ICI for a patient with MSI-H tumor. We review the potential causes and discuss the emerging literature regarding predictive factors of hyperprogression in the particular subset of MSI-H patients. If some data were available in retrospective studies, validation of strong predictive factors is needed to avoid such dramatic evolutions.

| S-EPMC8499695 | biostudies-literature

Optimizing immunotherapy for gynecologic cancers.

Project description:Purpose of reviewThis review will provide an update on the most recent clinical developments in immuno-oncology in advanced gynecologic cancers and will also highlight ongoing studies in this field.Recent findingsAlthough immune checkpoint blockade (ICB) therapy is rapidly altering the treatment landscape in a myriad of solid tumors, the efficacy of ICB therapy with antibodies directed against CTLA-4, PD-1, and PD-L1 in advanced gynecologic cancers has been limited. The exception has been the PD-1 inhibitor pembrolizumab in microsatellite instability high (MSI-H) or mismatch repair-deficient (dMMR) advanced endometrial cancers, highlighted by the recent conditional approval of pembrolizumab in recurrent/metastatic PD-L1-positive cervical cancers and the accelerated approval of pembrolizumab and lenvatinib in microsatellite stable (MSS) or mismatch repair-proficient (pMMR) advanced endometrial cancer. The discovery of novel, rational ICB combinatorial approaches in advanced gynecologic cancers is highly warranted.SummaryRecent advances in the genomic characterization of gynecologic malignancies have informed clinical trial design. However, improved molecular and immunophenotypic biomarkers to more accurately identify patients who will most benefit from immunotherapeutic approaches are urgently needed. This is especially critical as we attempt to integrate immune-oncology agents, chemotherapy, targeted therapy, and radiation therapy in the management of gynecologic cancers.

| S-EPMC8135258 | 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