Neoadjuvant triplet immune checkpoint blockade in newly diagnosed glioblastoma DOI Creative Commons
Georgina V. Long, Elena Shklovskaya, Laveniya Satgunaseelan

et al.

Nature Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

Abstract Glioblastoma (GBM) is an aggressive primary adult brain tumor that rapidly recurs after standard-of-care treatments, including surgery, chemotherapy and radiotherapy. While immune checkpoint inhibitor therapies have transformed outcomes in many types, particularly when used neoadjuvantly or as a first-line treatment, melanoma metastases, they shown limited efficacy patients with resected recurrent GBM. The lack of has been attributed to the scarcity tumor-infiltrating lymphocytes (TILs), immunosuppressive microenvironment low mutation burden typical GBM tumors, plus exclusion large molecules from parenchyma. We hypothesized upfront neoadjuvant combination immunotherapy, administered disease situ, could induce stronger response than treatment given resection recurrence. Here, we present case newly diagnosed IDH - wild-type, MGMT promoter unmethylated GBM, treated single dose triplet immunotherapy (anti-programmed cell death protein 1 anti-cytotoxic T-lymphocyte 4 anti-lymphocyte-activation gene 3) followed by maximal safe 12 days later. anti-programmed drug was bound TILs there marked TIL infiltration activation compared baseline biopsy. After 17 months, no definitive sign If first line, before resection, inhibitors are capable may response. A clinical trial therapy planned (GIANT; registration no. NCT06816927 ).

Language: Английский

Neoadjuvant immune checkpoint blockade: A window of opportunity to advance cancer immunotherapy DOI Creative Commons
Suzanne L. Topalian, Patrick M. Forde, Leisha A. Emens

et al.

Cancer Cell, Journal Year: 2023, Volume and Issue: 41(9), P. 1551 - 1566

Published: Aug. 17, 2023

Language: Английский

Citations

141
Dysregulation of ILC3s unleashes progression and immunotherapy resistance in colon cancer DOI Creative Commons
Jérémy Goc,

Mengze Lv,

Nicholas J. Bessman

et al.

Cell, Journal Year: 2021, Volume and Issue: 184(19), P. 5015 - 5030.e16

Published: Aug. 17, 2021

Language: Английский

Citations

140
Emerging concepts in PD-1 checkpoint biology DOI Creative Commons
Kristen E. Pauken, James A. Torchia, Apoorvi Chaudhri

et al.

Seminars in Immunology, Journal Year: 2021, Volume and Issue: 52, P. 101480 - 101480

Published: Feb. 1, 2021

The PD-1 pathway is a cornerstone in immune regulation. While the has received considerable attention for its role contributing to maintenance of T cell exhaustion chronic infection and cancer, plays diverse roles regulating host immunity beyond exhaustion. Here, we discuss emerging concepts pathway, including (1) impact inhibitors on differentiation states effector memory development during acute infection, as well (2) Treg cells, NK ILCs, (3) functions PD-L1/B7-1 PD-L2/RGMb/neogenin interactions. We then use neoadjuvant blockade treatment early-stage cancers how timing may improve clinical outcomes. binding partners associated ligands, broad expression patterns receptors differential modulation cells depending location state differentiation, add additional layers complexity are important considerations improving efficacy safety therapeutics.

Language: Английский

Citations

134
Multiomic profiling of checkpoint inhibitor-treated melanoma: Identifying predictors of response and resistance, and markers of biological discordance DOI Creative Commons
Felicity Newell, Inês Pires da Silva, Peter A. Johansson

et al.

Cancer Cell, Journal Year: 2021, Volume and Issue: 40(1), P. 88 - 102.e7

Published: Dec. 23, 2021

Language: Английский

Citations

115
The status of tumor mutational burden and immunotherapy DOI
Valsamo Anagnostou, Alberto Bardelli, Timothy A. Chan

et al.

Nature Cancer, Journal Year: 2022, Volume and Issue: 3(6), P. 652 - 656

Published: June 28, 2022

Language: Английский

Citations

107
Evolutionary patterns and research frontiers in neoadjuvant immunotherapy: a bibliometric analysis DOI Creative Commons
Shitao Jiang, Y. Liu, Han Zheng

et al.

International Journal of Surgery, Journal Year: 2023, Volume and Issue: unknown

Published: May 22, 2023

Research has shown that neoadjuvant immunotherapy may provide more significant clinical benefits to cancer patients undergoing surgery than adjuvant therapy. This study examines the development of research using bibliometric analysis. As February 12, 2023, articles on in Web Science Core Collection (WoSCC) were collected. Co-authorship and keyword co-occurrence analyses visualizations performed VOSviewer, while CiteSpace was used identify bursting keywords references. The analyzed a total 1,222 publications. top contributors this field United States (US), China, Italy, journal with most publications Frontiers Oncology. Francesco Montorsi had highest H-index. common “immunotherapy” “neoadjuvant therapy.” conducted analysis over 20 years research, identifying countries, institutions, authors, journals, involved field. findings comprehensive overview research.

Language: Английский

Citations

88
Survival update of neoadjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma in the OpACIN and OpACIN-neo trials DOI Creative Commons
Judith M. Versluis, Alexander M. Menzies, Karolina Sikorska

et al.

Annals of Oncology, Journal Year: 2023, Volume and Issue: 34(4), P. 420 - 430

Published: Jan. 18, 2023

Language: Английский

Citations

75
Localization, tissue biology and T cell state — implications for cancer immunotherapy DOI
Jason M. Schenkel, Kristen E. Pauken

Nature reviews. Immunology, Journal Year: 2023, Volume and Issue: 23(12), P. 807 - 823

Published: May 30, 2023

Language: Английский

Citations

66
Immunosurveillance in clinical cancer management DOI Open Access
Guido Kroemer, Timothy A. Chan, Alexander M.M. Eggermont

et al.

CA A Cancer Journal for Clinicians, Journal Year: 2023, Volume and Issue: 74(2), P. 187 - 202

Published: Oct. 25, 2023

The progression of cancer involves a critical step in which malignant cells escape from control by the immune system. Antineoplastic agents are particularly efficient when they succeed restoring such (immunosurveillance) or at least establish an equilibrium state that slows down disease progression. This is true not only for immunotherapies, as checkpoint inhibitors (ICIs), but also conventional chemotherapy, targeted anticancer agents, and radiation therapy. Thus, therapeutics stress kill while provoking tumor-targeting response, referred to immunogenic cell death, useful combination with ICIs. Modern oncology regimens increasingly using combinations, chemoimmunotherapy, well combinations multiple However, latter generally associated severe side effects compared single-agent Of note, success these combinatorial strategies against locally advanced metastatic cancers now spurring successful attempts move them past postoperative (adjuvant) setting preoperative (neoadjuvant) setting, even patients operable cancers. Here, authors critically discuss importance immunosurveillance modern clinical management.

Language: Английский

Citations

66
Neoadjuvant atezolizumab plus chemotherapy in gastric and gastroesophageal junction adenocarcinoma: the phase 2 PANDA trial DOI Creative Commons
Y.L. Verschoor, Joris van de Haar,

José G. van den Berg

et al.

Nature Medicine, Journal Year: 2024, Volume and Issue: 30(2), P. 519 - 530

Published: Jan. 8, 2024

Abstract Gastric and gastroesophageal junction (G/GEJ) cancers carry a poor prognosis, despite recent advancements, most patients die of their disease. Although immune checkpoint blockade became part the standard-of-care for with metastatic G/GEJ cancers, its efficacy impact on tumor microenvironment (TME) in early disease remain largely unknown. We hypothesized higher neoadjuvant immunotherapy plus chemotherapy nonmetastatic cancer. In phase 2 PANDA trial, previously untreated resectable tumors ( n = 21) received treatment one cycle atezolizumab monotherapy followed by four cycles docetaxel, oxaliplatin capecitabine. Treatment was well tolerated. There were grade 3 immune-related adverse events two 20 (10%) but no 4 or 5 events, all underwent resection without treatment-related delays, meeting primary endpoint safety feasibility. Tissue obtained at multiple time points, allowing analysis effects single-agent anti-programmed cell death ligand 1 (PD-L1) subsequent combination TME. Twenty 21 surgery evaluable secondary pathologic response survival endpoints, 19 exploratory translational analyses. A major (≤10% residual viable tumor) observed 14 (70%, 95% confidence interval 46–88%) patients, including 9 (45%, 23–68%) complete responses. At median follow-up 47 months, 13 responders alive disease-free, five six nonresponders had died as result recurrence. Notably, baseline protein (PD-1) + CD8 T infiltration significantly versus nonresponders, comparison TME alterations following anti-PD-L1 showed an increased activation PD-1/L1 axis blockade. On basis these data, before warrants further exploration validation larger cohort ClinicalTrials.gov registration: NCT03448835 .

Language: Английский

Citations

56