Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Immunotherapy for primary brain tumors: no longer a matter of privilege.

ABSTRACT: Immunotherapy for cancer continues to gain both momentum and legitimacy as a rational mode of therapy and a vital treatment component in the emerging era of personalized medicine. Gliomas, and their most malignant form, glioblastoma, remain as a particularly devastating solid tumor for which standard treatment options proffer only modest efficacy and target specificity. Immunotherapy would seem a well-suited choice to address such deficiencies given both the modest inherent immunogenicity of gliomas and the strong desire for treatment specificity within the confines of the toxicity-averse normal brain. This review highlights the caveats and challenges to immunotherapy for primary brain tumors, as well as reviewing modalities that are currently used or are undergoing active investigation. Tumor immunosuppressive countermeasures, peculiarities of central nervous system immune access, and opportunities for rational treatment design are discussed.

SUBMITTER: Fecci PE

PROVIDER: S-EPMC4235630 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Immunotherapy for primary brain tumors: no longer a matter of privilege.

Fecci Peter E PE Heimberger Amy B AB Sampson John H JH

Clinical cancer research : an official journal of the American Association for Cancer Research 20141101 22

Immunotherapy for cancer continues to gain both momentum and legitimacy as a rational mode of therapy and a vital treatment component in the emerging era of personalized medicine. Gliomas, and their most malignant form, glioblastoma, remain as a particularly devastating solid tumor for which standard treatment options proffer only modest efficacy and target specificity. Immunotherapy would seem a well-suited choice to address such deficiencies given both the modest inherent immunogenicity of gli ...[more]

PMID: 25398845

Similar Datasets

Immunotherapy of Primary Brain Tumors: Facts and Hopes.

Project description:The field of cancer immunotherapy has made exciting progress for some cancer types in recent years. However, recent failures of late-phase clinical trials evaluating checkpoint blockade in patients with glioblastoma (GBM) represent continued challenges for brain cancer immunotherapy. This is likely due to multiple factors including but not limited to marked genetic and antigenic heterogeneity, relatively low mutational loads, and paucity of GBM-infiltrating T cells. We review recent and ongoing studies targeting the checkpoint molecules as monotherapy or in combination with other modalities, and discuss the mechanisms underlying the unresponsiveness of GBM to single-modality immunotherapy approaches. We also discuss other novel immunotherapy approaches that may promote T-cell responses and overcome the "cold tumor" status of GBM, including oncolytic viruses and adoptive T-cell therapy. Clin Cancer Res; 24(21); 5198-205. ©2018 AACR.

| S-EPMC6214775 | biostudies-literature

Immunotherapy associated central nervous system complications in primary brain tumors.

Project description:Advances clarifying the genetics and function of the immune system within the central nervous system (CNS) and brain tumor microenvironment have led to increasing momentum and number of clinical trials using immunotherapy for primary brain tumors. While neurological complications of immunotherapy in extra-cranial malignancies is well described, the CNS toxicities of immunotherapy in patients with primary brain tumors with their own unique physiology and challenges are burgeoning. This review highlights the emerging and unique CNS complications associated with immunotherapy including checkpoint inhibitors, oncolytic viruses, adoptive cell transfer/chimeric antigen receptor (CAR) T cell and vaccines for primary brain tumors, as well as reviews modalities that have been currently employed or are undergoing investigation for treatment of such toxicities.

| S-EPMC9981156 | biostudies-literature

Immunotherapy for Pediatric Brain Tumors.

Project description:Malignant brain tumors are the most common cause of solid cancer death in children. New targeted therapies are vital to improve treatment outcomes, but must be developed to enable trafficking across the blood brain barrier (BBB). Since activated T cells cross the BBB, cancer immunotherapy can be harnessed to unlock the cytotoxic potential of the immune system. However, standard of care treatments (i.e., chemotherapy and radiation) applied concomitant to pediatric brain tumor immunotherapy may abrogate induction of immunotherapeutic responses. This review will discuss the development of immunotherapies within this paradigm using emerging approaches being investigated in phase I/II trials in children with refractory brain tumors, including checkpoint inhibitors, vaccine immunotherapy, and adoptive cell therapy.

| S-EPMC5664064 | biostudies-literature

The current state of immunotherapy for primary and secondary brain tumors: similarities and differences.

Project description:Treatment and resolution of primary and metastatic brain tumors have long presented a challenge to oncologists. In response to the dismal survival outcomes associated with conventional therapies, various immunotherapy modalities, such as checkpoint inhibitors, vaccine, cellular immunotherapy and viral immunotherapy have been actively explored over the past couple of decades. Although improved patient survival has been more frequently noted in treatment of brain metastases, little progress has been made in improving patient survival in cases of primary brain tumors, specifically glioblastoma, which is the representative primary brain tumor discussed in this review. Herein, we will first overview the findings of recent clinical studies for treatment of primary and metastatic brain tumors with immunotherapeutic interventions. The clinical efficacy of these immunotherapies will be discussed in the context of their ability or inability to overcome inherent characteristics of the tumor as well as restricted antigen presentation and its immunosuppressive microenvironment. Additionally, this review aims to briefly inform clinicians in the field of neuro-oncology on the relevant aspects of the immune system as it pertains to the central nervous system, with special focus on the differing modes of antigen presentation and tumor microenvironment of primary and metastatic brain tumors and the role these differences may play in the efficacy of immunotherapy in eradicating the tumor.

| S-EPMC7733526 | biostudies-literature

Immunotherapy for pediatric brain tumors: past and present.

Project description:The field of cancer immunotherapy has progressed at an accelerated rate over the past decade. Pediatric brain tumors thus far have presented a formidable challenge for immunotherapy development, given their typically low mutational burden, location behind the blood-brain barrier in a unique tumor microenvironment, and intratumoral heterogeneity. Despite these challenges, recent developments in the field have resulted in exciting preclinical evidence for various immunotherapies and multiple clinical trials. This work reviews the history and advances in active immunotherapy, checkpoint blockade, and adoptive T-cell therapy for pediatric brain tumors, including ongoing clinical trials.

| S-EPMC6784275 | biostudies-literature

Turning "Cold" Into "Hot" Tumors-Opportunities and Challenges for Radio-Immunotherapy Against Primary and Metastatic Brain Cancers.

Project description:The development of immunotherapies has revolutionized intervention strategies for a variety of primary cancers. Despite this promising progress, treatment options for primary brain cancer and brain metastasis remain limited and still largely depend on surgical resection, radio- and/or chemotherapy. The paucity in the successful development of immunotherapies for brain cancers can in part be attributed to the traditional view of the brain as an immunologically privileged site. The presence of the blood-brain barrier and the absence of lymphatic drainage were believed to restrict the entry of blood-borne immune and inflammatory cells into the central nervous system (CNS), leading to an exclusion of the brain from systemic immune surveillance. However, recent insight from pre-clinical and clinical studies on the immune landscape of brain cancers challenged this dogma. Recruitment of blood-borne immune cells into the CNS provides unprecedented opportunities for the development of tumor microenvironment (TME)-targeted or immunotherapies against primary and metastatic cancers. Moreover, it is increasingly recognized that in addition to genotoxic effects, ionizing radiation represents a critical modulator of tumor-associated inflammation and synergizes with immunotherapies in adjuvant settings. This review summarizes current knowledge on the cellular and molecular identity of tumor-associated immune cells in primary and metastatic brain cancers and discusses underlying mechanisms by which ionizing radiation modulates the immune response. Detailed mechanistic insight into the effects of radiation on the unique immune landscape of brain cancers is essential for the development of multimodality intervention strategies in which immune-modulatory effects of radiotherapy are exploited to sensitize brain cancers to immunotherapies by converting immunologically "cold" into "hot" environments.

| S-EPMC6433980 | biostudies-literature

Targeting oncometabolism to maximize immunotherapy in malignant brain tumors.

Project description:Brain tumors result in significant morbidity and mortality in both children and adults. Recent data indicate that immunotherapies may offer a survival benefit after standard of care has failed for malignant brain tumors. Modest results from several late phase clinical trials, however, underscore the need for more refined, comprehensive strategies that incorporate new mechanistic and pharmacologic knowledge. Recently, oncometabolism has emerged as an adjunct modality for combinatorial treatment approaches necessitated by the aggressive, refractory nature of high-grade glioma and other progressive malignant brain tumors. Manipulation of metabolic processes in cancer and immune cells that comprise the tumor microenvironment through controlled targeting of oncogenic pathways may be utilized to maximize the efficacy of immunotherapy and improve patient outcomes. Herein, we summarize preclinical and early phase clinical trial research of oncometabolism-based therapeutics that may augment immunotherapy by exploiting the biochemical and genetic underpinnings of brain tumors. We also examine metabolic pathways related to immune cells that target tumor cells, termed "tumor immunometabolism". Specifically, we focus on glycolysis and altered glucose metabolism, including glucose transporters, hexokinase, pyruvate dehydrogenase, and lactate dehydrogenase, glutamine, and we discuss targeting arginase, adenosine, and indoleamine 2,3-dioxygenase, and toll-like receptors. Lastly, we summarize future directions targeting metabolism in combination with emerging therapies such as oncolytic virotherapy, vaccines, and chimeric antigen receptor T cells.

| S-EPMC9081266 | biostudies-literature

Actionable molecular biomarkers in primary brain tumors.

Project description:Recent genome-wide studies of malignancies of the central nervous system (CNS) have revolutionized our understanding of the biology of these tumors. This newly gained knowledge provides a wealth of opportunity for biomarker driven clinical research. To date, however, only few of the available molecular markers truly influence clinical decision-making and treatment. The most widely validated markers in neuro-oncology presently are: 1) MGMT promoter methylation as a prognostic and predictive marker in glioblastoma, 2) co-deletion of 1p and 19q differentiating oligodendrogliomas from astrocytomas, 3) IDH1/2 mutations, and 4) select pathway-associated mutations. This article focuses on currently impactful biomarkers in adult and pediatric brain cancers and it provides a perspective on the direction of research in this field.

| S-EPMC5461965 | biostudies-other

Primary and metastatic breast tumors cross-talk to influence immunotherapy responses.

Project description:The presence of a tumor can alter host immunity systematically. The immune-tumor interaction in one site may impact the local immune microenvironment in distal tissues through the circulation, and therefore influence the efficacy of immunotherapies to distant metastases. Improved understanding of the immune-tumor interactions during immunotherapy treatment in a metastatic setting may enhance the efficacy of current immunotherapies. Here we investigate the response to αPD-1/αCTLA4 and trimAb (αDR5, α4-1BB, αCD40) of 67NR murine breast tumors grown simultaneously in the mammary fat pad (MFP) and lung, a common site of breast cancer metastasis, and compared to tumors grown in isolation. Lung tumors present in isolation were resistant to both therapies. However, in MFP and lung tumor-bearing mice, the presence of a MFP tumor could increase lung tumor response to immunotherapy and decrease the number of lung metastases, leading to complete eradication of lung tumors in a proportion of mice. The MFP tumor influence on lung metastases was mediated by CD8+ T cells, as CD8+ T cell depletion abolished the difference in lung metastases. Furthermore, mice with concomitant MFP and lung tumors had increased tumor specific, effector CD8+ T cells infiltration in the lungs. Thus, we propose a model where tumors in an immunogenic location can give rise to systemic anti-tumor CD8+ T cell responses that could be utilized to target metastatic tumors. These results highlight the requirement for clinical consideration of cross-talk between primary and metastatic tumors for effective immunotherapy for cancers otherwise resistant to immunotherapy.

| S-EPMC7470186 | biostudies-literature

Antibody, T-cell and dendritic cell immunotherapy for malignant brain tumors.

Project description:Modest improvement in brain tumor patient survival has been achieved through advances in surgical, adjuvant radiation and chemotherapeutic strategies. However, these traditional approaches have been unsuccessful in permanently controlling these aggressive tumors, with recurrence being quite common. Hence, there is a need for novel therapeutic approaches that specifically target the molecularly diverse brain tumor cell population. The ability of the immune system to recognize altered tumor cells while avoiding surrounding normal cells offers an enormous advantage over the nonspecific nature of the conventional treatment schemes. Therefore, immunotherapy represents a promising approach that may supplement the standard therapies in eliminating the residual brain tumor cells. This review summarizes different immunotherapeutic approaches currently being tested for malignant brain tumor treatment.

| S-EPMC3904373 | 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