Methionine deficiency facilitates antitumour immunity by altering m6A methylation of immune checkpoint transcripts DOI Creative Commons
Ting Li,

Yue‐Tao Tan,

Yan‐Xing Chen

et al.

Gut, Journal Year: 2022, Volume and Issue: 72(3), P. 501 - 511

Published: July 8, 2022

Objective Methionine metabolism is involved in a myriad of cellular functions, including methylation reactions and redox maintenance. Nevertheless, it remains unclear whether methionine metabolism, RNA antitumour immunity are molecularly intertwined. Design The effect methionine-restricted diet (MRD) feeding was assessed murine models. mechanisms YTH domain-containing family protein 1 (YTHDF1) tumour immune escape were determined vitro vivo. synergistic effects MRD or YTHDF1 depletion with PD-1 blockade also investigated. Results We found that dietary restriction reduced growth enhanced by increasing the number cytotoxicity tumour-infiltrating CD8 + T cells different mouse Mechanistically, S-adenosylmethionine derived from promoted N 6 -methyladenosine (m A) translation checkpoints, PD-L1 V-domain Ig suppressor cell activation (VISTA), cells. Furthermore, m A-specific binding inhibited restoring infiltration cells, synergised for better control. Clinically, expression correlated poor prognosis immunotherapy outcomes cancer patients. Conclusions play critical role anticancer through regulating functions Targeting could be potential new strategy immunotherapy.

Language: Английский

Advances in the development of personalized neoantigen-based therapeutic cancer vaccines DOI Open Access
Eryn Blass, Patrick A. Ott

Nature Reviews Clinical Oncology, Journal Year: 2021, Volume and Issue: 18(4), P. 215 - 229

Published: Jan. 20, 2021

Language: Английский

Citations

766
Mechanisms of immunotherapy resistance: lessons from glioblastoma DOI
Christopher M. Jackson, John Choi, Michael Lim

et al.

Nature Immunology, Journal Year: 2019, Volume and Issue: 20(9), P. 1100 - 1109

Published: July 29, 2019

Language: Английский

Citations

594
Brain immunology and immunotherapy in brain tumours DOI
John H. Sampson, Michael D. Gunn, Peter E. Fecci

et al.

Nature reviews. Cancer, Journal Year: 2019, Volume and Issue: 20(1), P. 12 - 25

Published: Dec. 5, 2019

Language: Английский

Citations

542
Interactions between cancer cells and immune cells drive transitions to mesenchymal-like states in glioblastoma DOI Creative Commons
Toshiro Hara, Rony Chanoch-Myers, Nathan D. Mathewson

et al.

Cancer Cell, Journal Year: 2021, Volume and Issue: 39(6), P. 779 - 792.e11

Published: June 1, 2021

Language: Английский

Citations

405
Emerging therapies for glioblastoma: current state and future directions DOI Creative Commons
Rong Liang, Ni Li, Zhenzhen Zhang

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2022, Volume and Issue: 41(1)

Published: April 15, 2022

Abstract Glioblastoma (GBM) is the most common high-grade primary malignant brain tumor with an extremely poor prognosis. Given survival currently approved treatments for GBM, new therapeutic strategies are urgently needed. Advances in decades of investment basic science glioblastoma rapidly translated into innovative clinical trials, utilizing improved genetic and epigenetic profiling as well microenvironment immune system interactions. Following these encouraging findings, immunotherapy including checkpoint blockade, chimeric antigen receptor T (CAR T) cell therapy, oncolytic virotherapy, vaccine therapy have offered hope improving GBM outcomes; ongoing studies using combinatorial therapies aim minimizing adverse side-effects augmenting antitumor responses. In addition, techniques to overcome blood-brain barrier (BBB) targeted delivery being tested trials patients recurrent GBM. Here, we set forth rationales promising treating review potential novel agents, current status preclinical discuss challenges future perspectives immuno-oncology.

Language: Английский

Citations

334
Turning cold tumors hot: from molecular mechanisms to clinical applications DOI
Jiahui Zhang, Di Huang, Phei Er Saw

et al.

Trends in Immunology, Journal Year: 2022, Volume and Issue: 43(7), P. 523 - 545

Published: May 25, 2022

Language: Английский

Citations

334
Phase III trial of chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated MGMT promoter DOI Creative Commons
Michael Lim, Michael Weller, Ahmed Idbaïh

et al.

Neuro-Oncology, Journal Year: 2022, Volume and Issue: 24(11), P. 1935 - 1949

Published: April 28, 2022

Abstract Background Nearly all patients with newly diagnosed glioblastoma experience recurrence following standard-of-care radiotherapy (RT) + temozolomide (TMZ). The purpose of the phase III randomized CheckMate 548 study was to evaluate RT TMZ combined immune checkpoint inhibitor nivolumab (NIVO) or placebo (PBO) in methylated MGMT promoter (NCT02667587). Methods Patients (N = 716) were 1:1 NIVO [(240 mg every 2 weeks × 8, then 480 4 weeks) (60 Gy over 6 (75 mg/m2 once daily during RT, 150-200 on days 1-5 28-day cycle 6)] PBO same regimen. primary endpoints progression-free survival (PFS) and overall (OS) without baseline corticosteroids patients. Results As December 22, 2020, median (m)PFS (blinded independent central review) 10.6 months (95% CI, 8.9-11.8) vs 10.3 9.7-12.5) (HR, 1.1; 95% 0.9-1.3) mOS 28.9 24.4-31.6) 32.1 29.4-33.8), respectively 0.9-1.3). In corticosteroids, 31.3 28.6-34.8) 33.0 31.0-35.1) 0.9-1.4). Grade 3/4 treatment-related adverse event rates 52.4% 33.6%, respectively. Conclusions added did not improve indeterminate promoter. No new safety signals observed.

Language: Английский

Citations

317
Glioma progression is shaped by genetic evolution and microenvironment interactions DOI Creative Commons
Frederick S. Varn, Kevin C. Johnson, Jan Martínek

et al.

Cell, Journal Year: 2022, Volume and Issue: 185(12), P. 2184 - 2199.e16

Published: May 31, 2022

Language: Английский

Citations

309
CRISPR-Cas9 disruption of PD-1 enhances activity of universal EGFRvIII CAR T cells in a preclinical model of human glioblastoma DOI Creative Commons
Bryan D. Choi, Xiaoling Yu, Ana P. Castaño

et al.

Journal for ImmunoTherapy of Cancer, Journal Year: 2019, Volume and Issue: 7(1)

Published: Nov. 14, 2019

Despite remarkable success in the treatment of hematological malignancies, CAR T-cell therapies for solid tumors have floundered, large part due to local immune suppression and effects prolonged stimulation leading dysfunction exhaustion. One mechanism by which gliomas other cancers can hamper T cells is through surface expression inhibitory ligands such as programmed cell death ligand 1 (PD-L1). Using CRIPSR-Cas9 system, we created universal resistant PD-1 inhibition multiplexed gene disruption endogenous receptor (TRAC), beta-2 microglobulin (B2M) (PDCD1). Triple gene-edited demonstrated enhanced activity preclinical glioma models. Prolonged survival mice bearing intracranial was achieved after intracerebral, but not intravenous administration. CRISPR-Cas9 gene-editing only provides a potential source allogeneic, donor cells, also enables simultaneous checkpoint signaling that otherwise impedes maximal antitumor functionality.

Language: Английский

Citations

240
Understanding the glioblastoma immune microenvironment as basis for the development of new immunotherapeutic strategies DOI Creative Commons
Ana Rita Pombo Antunes, Isabelle Scheyltjens, Johnny Duerinck

et al.

eLife, Journal Year: 2020, Volume and Issue: 9

Published: Feb. 4, 2020

Cancer immunotherapy by immune checkpoint blockade has proven its great potential saving the lives of a proportion late stage patients with immunogenic tumor types. However, even in these sensitive types, majority do not sufficiently respond to therapy. Furthermore, other including glioblastoma, remain largely refractory. The glioblastoma microenvironment is recognized as highly immunosuppressive, posing major hurdle for inducing immune-mediated destruction cancer cells. Scattered information available about presence and activity immunosuppressive or immunostimulatory cell types tumors, tumor-associated macrophages, tumor-infiltrating dendritic cells regulatory T These are heterogeneous at level ontogeny, spatial distribution functionality within compartment, providing insight complex cellular molecular interplay that determines refractory state glioblastoma. This knowledge may also yield next generation targets therapeutic intervention.

Language: Английский

Citations

232