Tumor-infiltrating lymphocytes in the immunotherapy era

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

Published: Nov. 2, 2020

Language: Английский

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Natural killer cells in antitumour adoptive cell immunotherapy

Nature reviews. Cancer, Journal Year: 2022, Volume and Issue: 22(10), P. 557 - 575

Published: July 25, 2022

Language: Английский

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The NK cell–cancer cycle: advances and new challenges in NK cell–based immunotherapies

Nature Immunology, Journal Year: 2020, Volume and Issue: 21(8), P. 835 - 847

Published: July 20, 2020

Language: Английский

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Therapeutic targets and biomarkers of tumor immunotherapy: response versus non-response

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Sept. 19, 2022

Abstract Cancers are highly complex diseases that characterized by not only the overgrowth of malignant cells but also an altered immune response. The inhibition and reprogramming system play critical roles in tumor initiation progression. Immunotherapy aims to reactivate antitumor overcome escape mechanisms tumors. Represented checkpoint blockade adoptive cell transfer, immunotherapy has seen tremendous success clinic, with capability induce long-term regression some tumors refractory all other treatments. Among them, blocking therapy, represented PD-1/PD-L1 inhibitors (nivolumab) CTLA-4 (ipilimumab), shown encouraging therapeutic effects treatment various tumors, such as non-small lung cancer (NSCLC) melanoma. In addition, advent CAR-T, CAR-M novel methods, entered a new era. At present, evidence indicates combination multiple methods may be one way improve effect. However, overall clinical response rate still needs improvement, which warrants development designs well discovery biomarkers can guide prescription these agents. Learning from past failure both basic research is for rational design studies future. this article, we describe efforts manipulate against discuss different targets types exploited promote

Language: Английский

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Immune checkpoint therapy for solid tumours: clinical dilemmas and future trends

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Aug. 28, 2023

Abstract Immune-checkpoint inhibitors (ICBs), in addition to targeting CTLA-4, PD-1, and PD-L1, novel LAG-3 drugs have also been approved clinical application. With the widespread use of drug, we must deeply analyze dilemma agents seek a breakthrough treatment prospect. Over past decades, these demonstrated dramatic efficacy, especially patients with melanoma non-small cell lung cancer (NSCLC). Nonetheless, field broad concept solid tumours, non-specific indications, inseparable immune response side effects, unconfirmed progressive disease, complex regulatory networks resistance are four barriers that limit its Fortunately, successful trials ICB combination therapies, advent era oncolytic virus gene editing, technical mRNA vaccines nano-delivery systems made remarkable breakthroughs currently. In this review, enumerate mechanisms each checkpoint targets, associations between tumour mutation burden, key or signalling pathways, specific evidence efficacy classical targets new among different types put forward dialectical thoughts on drug safety. Finally, discuss importance accurate triage based recent advances predictive biomarkers diagnostic testing techniques.

Language: Английский

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Cancer immunotherapy with γδ T cells: many paths ahead of us

Cellular and Molecular Immunology, Journal Year: 2020, Volume and Issue: 17(9), P. 925 - 939

Published: July 22, 2020

γδ T cells play uniquely important roles in stress surveillance and immunity for infections carcinogenesis. Human recognize kill transformed independently of human leukocyte antigen (HLA) restriction, which is an essential feature conventional αβ cells. Vγ9Vδ2 cells, prevail the peripheral blood healthy adults, are activated by microbial or endogenous tumor-derived pyrophosphates a mechanism dependent on butyrophilin molecules. expressing other cell receptor variable genes, notably Vδ1, more abundant mucosal tissue. In addition to receptor, usually express activating natural killer (NK) receptors, such as NKp30, NKp44, NKG2D binds stress-inducible surface molecules that absent but frequently expressed malignant Therefore, endowed with at least two independent recognition systems sense tumor initiate anticancer effector mechanisms, including cytokine production cytotoxicity. view their HLA-independent potent antitumor activity, there has been increasing interest translating unique potential into innovative cellular cancer immunotherapies. Here, we discuss recent developments enhance efficacy cell-based immunotherapy. This includes strategies vivo activation tumor-targeting optimization vitro expansion protocols, development gene-modified It equally consider synergisms therapeutic strategies, checkpoint inhibitors, chemotherapy, (local) innate immunity.

Language: Английский

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COAST: An Open-Label, Phase II, Multidrug Platform Study of Durvalumab Alone or in Combination With Oleclumab or Monalizumab in Patients With Unresectable, Stage III Non–Small-Cell Lung Cancer

Journal of Clinical Oncology, Journal Year: 2022, Volume and Issue: 40(29), P. 3383 - 3393

Published: April 22, 2022

Durvalumab significantly improves overall survival for patients with unresectable stage III non-small-cell lung cancer and no progression after concurrent chemoradiotherapy (cCRT). Building upon that standard of care, COAST is a phase II study durvalumab alone or combined the anti-CD73 monoclonal antibody oleclumab anti-NKG2A monalizumab as consolidation therapy in this setting.Patients cancer, Eastern Cooperative Oncology Group performance status 0/1, cCRT were randomly assigned 1:1:1, ≤ 42 days post-cCRT, to up 12 months, stratified by histology. The primary end point was investigator-assessed confirmed objective response rate (ORR; RECIST v1.1).Between January 2019 July 2020, 189 assigned. At interim analysis (data cutoff, May 17, 2021), median follow-up 11.5 months (range, 0.4-23.4 months; all patients). Confirmed ORR numerically higher plus (30.0%; 95% CI, 18.8 43.2) (35.5%; 23.7 48.7) versus (17.9%; 9.6 29.2). Progression-free (PFS) prolonged both combinations (plus oleclumab: hazard ratio, 0.44; 0.26 0.75; monalizumab: 0.42; 0.24 0.72), 12-month PFS rates 62.6% [95% 48.1 74.2] 72.7% 58.8 82.6] v alone: 33.9% 21.2 47.1]). All-cause grade ≥ 3 treatment-emergent adverse events occurred 40.7%, 27.9%, 39.4% oleclumab, monalizumab, durvalumab, respectively.Both increased alone. Safety similar across arms new significant safety signals identified either combination. These data support their further evaluation trial.

Language: Английский

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Neoadjuvant atezolizumab for resectable non-small cell lung cancer: an open-label, single-arm phase II trial

Nature Medicine, Journal Year: 2022, Volume and Issue: 28(10), P. 2155 - 2161

Published: Sept. 12, 2022

In an ongoing, open-label, single-arm phase II study ( NCT02927301 ), 181 patients with untreated, resectable, stage IB-IIIB non-small cell lung cancer received two doses of neoadjuvant atezolizumab monotherapy. The primary end point was major pathological response (MPR; ≤10% viable malignant cells) in resected tumors without EGFR or ALK alterations. Of the 143 analysis, MPR 20% (95% confidence interval, 14-28%). With a minimum duration follow-up 3 years, 3-year survival rate 80% encouraging. most common adverse events during were fatigue (39%, 71 181) and procedural pain (29%, 53 181), along expected immune-related toxicities; there no unexpected safety signals. exploratory analyses, predicted using pre-treatment peripheral blood immunophenotype based on 14 immune subsets. Immune subsets predictive also identified tumor microenvironment associated MPR. This large cohort resectable safe met its ≥ 15%. Data from this single-arm, non-randomized trial suggest that profiles innate cells may predict after atezolizumab, but additional studies are needed to determine whether these can inform patient selection new therapeutic approaches.

Language: Английский

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Microstructure, pathophysiology, and potential therapeutics of COVID‐19: A comprehensive review

Journal of Medical Virology, Journal Year: 2020, Volume and Issue: 93(1), P. 275 - 299

Published: July 3, 2020

There have been over seven million cases and almost 413 372 deaths globally due to the novel coronavirus (2019-nCoV) associated disease COVID-19, as of 11 June 2020. Phylogenetic analysis suggests that there is a common source for these infections. The overall sequence similarities between spike protein 2019-nCoV SARS-CoV are known be around 76% 78% 73% whole receptor-binding domain (RBD), respectively. Thus, they potential serve drug and/or vaccine candidate. However, individual response against differs genetic variations in human population. Understanding angiotensin-converting enzyme 2 (ACE2) leukocyte antigen (HLA) may affect severity infection could help identifying individuals at higher risk from COVID-19. A number drugs/vaccines well antibody/cytokine-based therapeutics various developmental stages preclinical/clinical trials SARS-CoV, MERS-CoV, with substantial cross-reactivity, used For diagnosis, reverse-transcription polymerase chain reaction gold standard test initial diagnosis kit based on serological tests also recommended investigating spread COVID-19 but this challenging antibodies cross-reactivity. This review comprehensively summarizes recent reports available regarding host-pathogen interaction, morphological genomic structure virus, diagnostic techniques

Language: Английский

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Revealing the transcriptional heterogeneity of organ‐specific metastasis in human gastric cancer using single‐cell RNA Sequencing

Clinical and Translational Medicine, Journal Year: 2022, Volume and Issue: 12(2)

Published: Feb. 1, 2022

Abstract Background Deciphering intra‐ and inter‐tumoural heterogeneity is essential for understanding the biology of gastric cancer (GC) its metastasis identifying effective therapeutic targets. However, characteristics different organ‐tropism metastases GC are largely unknown. Methods Ten fresh human tissue samples from six patients, including primary tumour adjacent non‐tumoural organs or tissues (liver, peritoneum, ovary, lymph node) were evaluated using single‐cell RNA sequencing. Validation experiments performed histological assays bulk transcriptomic datasets. Results Malignant epithelial subclusters associated with invasion features, intraperitoneal propensity, epithelial–mesenchymal transition‐induced stem cell phenotypes, dormancy‐like discovered. High expression first three subcluster‐associated genes displayed worse overall survival than those low in a cohort containing 407 samples. Immune stromal cells exhibited cellular created pro‐tumoural immunosuppressive microenvironment. Furthermore, 20‐gene signature node‐derived exhausted CD8 + T was acquired to forecast node validated cohorts. Additionally, although anti‐NKG2A (KLRC1) antibody have not been used treat patients even clinical trials, we uncovered only malignant but one endothelial subcluster, mucosal‐associated invariant cells, cell‐like B plasmacytoid dendritic macrophages, monocytes, neutrophils may contribute HLA‐E‐KLRC1/KLRC2 interaction cytotoxic/exhausted and/or natural killer (NK) suggesting novel opportunities GC. our findings suggested that PD‐1 might predict responses blockade therapy Conclusions This study provided insights into heterogeneous microenvironment tumours organ‐specific provide support precise diagnosis treatment.

Language: Английский

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