Trial watch: chemotherapy-induced immunogenic cell death in immuno-oncology DOI Creative Commons
Isaure Vanmeerbeek, Jenny Sprooten, Dirk De Ruysscher

et al.

OncoImmunology, Journal Year: 2020, Volume and Issue: 9(1)

Published: Jan. 1, 2020

The term ‘immunogenic cell death’ (ICD) denotes an immunologically unique type of regulated death that enables, rather than suppresses, T cell-driven immune responses are specific for antigens derived from the dying cells. ability ICD to elicit adaptive immunity heavily relies on immunogenicity cells, implying such cells must encode and present not covered by central tolerance (antigenicity), deliver immunostimulatory molecules as damage-associated molecular patterns cytokines (adjuvanticity). Moreover, host system be equipped detect antigenicity adjuvanticity As cancer (but normal) express several tolerance, they can driven into some therapeutic agents, including limited to) chemotherapeutics anthracycline family, oxaliplatin bortezomib, well radiation therapy. In this Trial Watch, we describe current trends in preclinical clinical development ICD-eliciting chemotherapy partner immunotherapy, with a focus trials assessing efficacy context immunomonitoring.

Language: Английский

Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors DOI
Lorenzo Galluzzi, Juliette Humeau, Aitziber Buqué

et al.

Nature Reviews Clinical Oncology, Journal Year: 2020, Volume and Issue: 17(12), P. 725 - 741

Published: Aug. 5, 2020

Language: Английский

Citations

1024
Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial DOI
Elizabeth A. Mittendorf, Hong Zhang, Carlos H. Barrios

et al.

The Lancet, Journal Year: 2020, Volume and Issue: 396(10257), P. 1090 - 1100

Published: Sept. 20, 2020

Language: Английский

Citations

858
Consensus guidelines for the definition, detection and interpretation of immunogenic cell death DOI Creative Commons
Lorenzo Galluzzi, Ilio Vitale, Sarah H. Warren

et al.

Journal for ImmunoTherapy of Cancer, Journal Year: 2020, Volume and Issue: 8(1), P. e000337 - e000337

Published: March 1, 2020

Cells succumbing to stress via regulated cell death (RCD) can initiate an adaptive immune response associated with immunological memory, provided they display sufficient antigenicity and adjuvanticity. Moreover, multiple intracellular microenvironmental features determine the propensity of RCD drive immunity. Here, we provide updated operational definition immunogenic (ICD), discuss key factors that dictate ability dying cells response, summarize experimental assays are currently available for assessment ICD in vitro vivo, formulate guidelines their interpretation.

Language: Английский

Citations

855
High tumor mutation burden fails to predict immune checkpoint blockade response across all cancer types DOI Creative Commons
Daniel J. McGrail,

P.G. Pilié,

N.U. Rashid

et al.

Annals of Oncology, Journal Year: 2021, Volume and Issue: 32(5), P. 661 - 672

Published: March 18, 2021

•TMB-H failed to predict improved or clinically relevant response ICB in all cancer types.•Cancer types where TMB-H does not generally show no relationship between tumor neoantigen load and CD8 T-cell infiltration.•Further studies should be carried out before application of as a biomarker for types. BackgroundHigh mutation burden (TMB-H) has been proposed predictive immune checkpoint blockade (ICB), largely due the potential mutations generate immunogenic neoantigens. Despite recent pan-cancer approval treatment any tumor, assessed by targeted FoundationOne CDx assay nine types, utility this fully demonstrated across cancers.Patients methodsData from over 10 000 patient tumors included The Cancer Genome Atlas were used compare approaches determine TMB identify correlation predicted T cells. Association with outcomes was analyzed both objective rates (ORRs, N = 1551) overall survival (OS, 1936).ResultsIn levels positively correlated load, such melanoma, lung, bladder cancers, exhibited 39.8% ORR [95% confidence interval (CI) 34.9-44.8], which significantly higher than that observed low (TMB-L) [odds ratio (OR) 4.1, 95% CI 2.9-5.8, P < 2 × 10−16]. In showed breast cancer, prostate glioma, achieve 20% (ORR 15.3%, 9.2-23.4, 0.95), lower relative TMB-L (OR 0.46, 0.24-0.88, 0.02). Bulk ORRs different two categories (P 0.10) cohorts assessed. Equivalent results obtained analyzing OS treating continuous variable.ConclusionsOur analysis support solid Further type-specific are warranted. High cancers. Data 1936). variable. Our

Language: Английский

Citations

824
Treatment landscape of triple-negative breast cancer — expanded options, evolving needs DOI
Giampaolo Bianchini, Carmine De Angelis, Luca Licata

et al.

Nature Reviews Clinical Oncology, Journal Year: 2021, Volume and Issue: 19(2), P. 91 - 113

Published: Nov. 9, 2021

Language: Английский

Citations

809
Detection of immunogenic cell death and its relevance for cancer therapy DOI Creative Commons
Jitka Fučíková, Oliver Kepp, Lenka Kašíková

et al.

Cell Death and Disease, Journal Year: 2020, Volume and Issue: 11(11)

Published: Nov. 26, 2020

Abstract Chemotherapy, radiation therapy, as well targeted anticancer agents can induce clinically relevant tumor-targeting immune responses, which critically rely on the antigenicity of malignant cells and their capacity to generate adjuvant signals. In particular, immunogenic cell death (ICD) is accompanied by exposure release numerous damage-associated molecular patterns (DAMPs), altogether confer a robust adjuvanticity dying cancer cells, they favor recruitment activation antigen-presenting cells. ICD-associated DAMPs include surface-exposed calreticulin (CALR) secreted ATP, annexin A1 (ANXA1), type I interferon, high-mobility group box 1 (HMGB1). Additional hallmarks ICD encompass phosphorylation eukaryotic translation initiation factor 2 subunit-α (EIF2S1, better known eIF2α), autophagy, global arrest in transcription translation. Here, we outline methodological approaches for measuring markers vitro ex vivo discovery next-generation antineoplastic agents, development personalized regimens, identification optimal therapeutic combinations clinical management cancer.

Language: Английский

Citations

749
Tumor-infiltrating lymphocytes in the immunotherapy era DOI Open Access

Sterre T. Paijens,

Annegé Vledder, Marco de Bruyn

et al.

Cellular and Molecular Immunology, Journal Year: 2020, Volume and Issue: 18(4), P. 842 - 859

Published: Nov. 2, 2020

Language: Английский

Citations

651
Improving cancer immunotherapy using nanomedicines: progress, opportunities and challenges DOI
John D. Martin, Horacio Cabral, Triantafyllos Stylianopoulos

et al.

Nature Reviews Clinical Oncology, Journal Year: 2020, Volume and Issue: 17(4), P. 251 - 266

Published: Feb. 7, 2020

Language: Английский

Citations

544
Role of Immunotherapy in Triple-Negative Breast Cancer DOI Open Access
Tanya E. Keenan, Sara M. Tolaney

Journal of the National Comprehensive Cancer Network, Journal Year: 2020, Volume and Issue: 18(4), P. 479 - 489

Published: April 1, 2020

Immune checkpoint inhibitors (ICIs) have led to durable clinical remissions in many metastatic cancers. However, the single-agent efficacy of ICIs breast cancer is low, including triple-negative (TNBC), which has several key characteristics that enhance ICI responses. Strategies improve anticancer immune responses TNBC are urgently needed extend survival for patients with disease. This review presents monotherapy response rates and discusses combination strategies chemotherapy, targeted therapies, novel immunotherapies. It concludes a summary immunotherapy biomarkers call action future directions research critical advancing TNBC.

Language: Английский

Citations

454
Triple‑negative breast cancer therapy: Current and future perspectives (Review) DOI Creative Commons

Kwang‐Ai Won,

Charles Spruck

International Journal of Oncology, Journal Year: 2020, Volume and Issue: 57(6), P. 1245 - 1261

Published: Oct. 16, 2020

Triple‑negative breast cancer (TNBC) accounts for 10‑15% of all cases. TNBCs lack estrogen and progesterone receptors express low levels HER2, therefore do not respond to hormonal or anti‑HER2 therapies. TNBC is a particularly aggressive form that generally displays poorer prognosis compared other subtypes. chemotherapy sensitive, this treatment remains the standard care despite its limited benefit. Recent advances with novel agents have been made specific subgroups PD‑L1+ tumors germline Brca‑mutated tumors. However, only fraction these patients responds immune checkpoint PARP inhibitors even those who often develop resistance relapse. Various new combination strategies explored further understand molecular immunological aspects TNBC. In review, we discuss clinical trials in management as well perspectives potential future treatments.

Language: Английский

Citations

358