Cancer immunotherapies: advances and bottlenecks

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Aug. 24, 2023

Immunotherapy has ushered in a new era cancer treatment, and immunotherapy continues to be rejuvenated. The clinical goal of is prime host immune system provide passive or active immunity against malignant tumors. Tumor infiltrating leukocytes (TILs) play an immunomodulatory role tumor microenvironment (TME) which closely related escape cells, thus influence progress. Several immunotherapies, include checkpoint inhibitors (ICIs), vaccine, adoptive cell transfer (ACT), have shown great efficacy promise. In this review, we will summarize the recent research advances immunotherapy, including molecular mechanisms effects as well limitations immunotherapy.

Language: Английский

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Co-inhibition of TIGIT and PD-1/PD-L1 in Cancer Immunotherapy: Mechanisms and Clinical Trials

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: June 8, 2023

Abstract Over the past decade, immune checkpoint inhibitors (ICIs) have emerged as a revolutionary cancer treatment modality, offering long-lasting responses and survival benefits for substantial number of patients. However, response rates to ICIs vary significantly among individuals types, with notable proportion patients exhibiting resistance or showing no response. Therefore, dual ICI combination therapy has been proposed potential strategy address these challenges. One targets is TIGIT, an inhibitory receptor associated T-cell exhaustion. TIGIT diverse immunosuppressive effects on immunity cycle, including inhibition natural killer cell effector function, suppression dendritic maturation, promotion macrophage polarization M2 phenotype, differentiation T cells regulatory cells. Furthermore, linked PD-1 expression, it can synergize PD-1/PD-L1 blockade enhance tumor rejection. Preclinical studies demonstrated co-inhibition in enhancing anti-tumor improving outcomes several types. Several clinical trials are underway evaluate safety efficacy various results awaited. This review provides overview mechanisms treatment, summarizes latest investigating this therapy, discusses its prospects. Overall, represents promising therapeutic approach that improve treated ICIs.

Language: Английский

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Recent Advances and Challenges in Cancer Immunotherapy

Cancers, Journal Year: 2022, Volume and Issue: 14(16), P. 3972 - 3972

Published: Aug. 17, 2022

Cancer immunotherapy has revolutionized the field of oncology in recent years. Harnessing immune system to treat cancer led a large growth number novel immunotherapeutic strategies, including checkpoint inhibition, chimeric antigen receptor T-cell therapy and vaccination. In this review, we will discuss current landscape immuno-oncology research, with focus on elements that influence outcomes. We also highlight advances basic aspects tumor immunology, particular, role immunosuppressive cells within microenvironment regulating antitumor immunity. Lastly, how understanding immunology can lead development new strategies.

Language: Английский

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Targeting toll-like receptor 7/8 for immunotherapy: recent advances and prospectives

Biomarker Research, Journal Year: 2022, Volume and Issue: 10(1)

Published: Dec. 7, 2022

Abstract Toll-like receptors (TLRs) are a large family of proteins that expressed in immune cells and various tumor cells. TLR7/8 located the intracellular endosomes, participate surveillance play different roles growth. Activation TLRs 7 8 triggers induction Th1 type innate response highly sophisticated process immunity signaling with recent research advances involving small molecule activation TLR 8. The wide range expression clinical significance TLR7/TLR8 kinds cancers have been extensively explored. can be used as novel diagnostic biomarkers, progression prognostic indicators, immunotherapeutic targets for tumors. Although mechanism action cancer immunotherapy is still incomplete, on T involved regulation cell function serve co-stimulatory molecules activate immunity. agonists cell-mediated antitumor responses both adaptive to improve therapy. Recently, drugs TLR7 or TLR8 scaffolds developed. These lead certain cytokines chemokines applied treatment some diseases good adjutants vaccines. Furthermore, potential therapeutics tumor-targeted In this review, we summarize development strategies targeting patients chronic hepatitis B.

Language: Английский

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SKYSCRAPER-02: Tiragolumab in Combination With Atezolizumab Plus Chemotherapy in Untreated Extensive-Stage Small-Cell Lung Cancer

Journal of Clinical Oncology, Journal Year: 2023, Volume and Issue: 42(3), P. 324 - 335

Published: Nov. 17, 2023

The phase III SKYSCRAPER-02 study determined whether the benefits of atezolizumab plus carboplatin and etoposide (CE) could be enhanced by addition tiragolumab in untreated extensive-stage small-cell lung cancer (ES-SCLC). We report final progression-free survival (PFS) overall (OS) analyses.

Language: Английский

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SHP2: A Pleiotropic Target at the Interface of Cancer and Its Microenvironment

Cancer Discovery, Journal Year: 2023, Volume and Issue: 13(11), P. 2339 - 2355

Published: Sept. 8, 2023

Abstract The protein phosphatase SHP2/PTPN11 has been reported to be a key modulator of proliferative pathways in wide range malignancies. Intriguingly, SHP2 also described as critical regulator the tumor microenvironment. Based on this evidence is considered multifaceted target cancer, spurring notion that development direct inhibitors would provide twofold benefit intrinsic and extrinsic inhibition. In review, we will discuss role cancer microenvironment, clinical strategies which are leveraged combination agents improve therapeutic response. Significance: functions pleiotropic factor, its inhibition not only hinders growth but reshapes Although their single-agent activity may limited, hold potential being enhance depth durability response therapy.

Language: Английский

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Anti-TIGIT antibody improves PD-L1 blockade through myeloid and Treg cells

Nature, Journal Year: 2024, Volume and Issue: 627(8004), P. 646 - 655

Published: Feb. 28, 2024

Tiragolumab, an anti-TIGIT antibody with active IgG1κ Fc, demonstrated improved outcomes in the phase 2 CITYSCAPE trial (ClinicalTrials.gov: NCT03563716 ) when combined atezolizumab (anti-PD-L1) versus alone

Language: Английский

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Targeting TIGIT for cancer immunotherapy: recent advances and future directions

Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Jan. 16, 2024

Abstract As a newly identified checkpoint, T cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif (ITIM) domain (TIGIT) is highly expressed on CD4 + cells, CD8 natural killer (NK) regulatory cells (Tregs), tumor-infiltrating lymphocytes (TILs). TIGIT has been associated NK exhaustion in vivo individuals various cancers. It not only modulates survival but also mediates exhaustion. the primary ligand of humans, CD155 may be main target for immunotherapy due to its interaction TIGIT. found that anti-programmed death protein 1 (PD-1) treatment response cancer correlated Anti-TIGIT alone combination anti-PD-1 agents have tested immunotherapy. Although two clinical studies advanced lung had positive results, TIGIT-targeted antibody, tiragolumab, recently failed new trials. In this review, we highlight current developments discuss characteristics functions

Language: Английский

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Recent developments in immunotherapy for gastrointestinal tract cancers

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: Aug. 9, 2024

The past few decades have witnessed the rise of immunotherapy for Gastrointestinal (GI) tract cancers. role immune checkpoint inhibitors (ICIs), particularly programmed death protein 1 (PD-1) and PD ligand-1 antibodies, has become increasingly pivotal in treatment advanced perioperative GI Currently, anti-PD-1 plus chemotherapy is considered as first-line regimen unselected gastric/gastroesophageal junction adenocarcinoma (G/GEJC), mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer (CRC), esophageal (EC). In addition, encouraging performance claudin18.2-redirected chimeric antigen receptor T-cell (CAR-T) therapy later-line cancers brings new hope cell solid tumour treatment. Nevertheless, remains yet precise, researchers are dedicated to further maximising optimising efficacy. This review summarises important research, latest progress, future directions including EC, G/GEJC, CRC.

Language: Английский

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Anti-TIGIT Antibody Tiragolumab Alone or With Atezolizumab in Patients With Advanced Solid Tumors

JAMA Oncology, Journal Year: 2023, Volume and Issue: 9(11), P. 1574 - 1574

Published: Sept. 28, 2023

Importance Inhibition of the T-cell immunoreceptor with Ig and ITIM domains (TIGIT)/poliovirus receptor pathway may amplify antitumor immune response atezolizumab in programmed death ligand 1–selected tumors. Objective To evaluate safety activity anti-TIGIT antibody tiragolumab its combination patients advanced solid Design, Setting, Participants The GO30103 open-label, first-in-human phase 1a/1b dose-escalation dose-expansion nonrandomized controlled trial was conducted at 13 sites 6 countries (Australia, Canada, France, Korea, Spain, US). start dates were May 23, 2016, for 1a October 11, 1b. Patients aged 18 years or older measurable disease baseline. clinical cutoff date 1, 2021. Data analysis performed on January 24, 2022. Interventions received fixed-dose intravenous day 1 each 21-day cycle (2 mg escalating to 1200 mg) 1a, plus (1200 every 3 weeks) treated until progression, loss benefit, development unacceptable toxicity. Main Outcomes Measures primary end points included safety, tolerability, recommended 2 dose (RP2D) atezolizumab. secondary point investigator-assessed objective rate (ORR). Counts percentages are used categorical variables, medians ranges continuous variables. Results Among (n = 24) 1b 49) cohorts, median age 60 (range, 40-77) 54 25-81) years, respectively. More than half women (14 24 [58%] 25 49 [51%]), more a third (10 [42%] [37%]) had 4 prior cancer therapies. No dose-limiting toxicities occurred, maximum tolerated not reached (NR). most frequent treatment-related adverse events (AEs) fatigue (5 [21%]) pruritus [10%]) 1b; majority AEs grade 2. Immune-mediated occurred (17%) 29 (59%) during phases 1b, respectively (primarily 2). RP2D 600 intravenously weeks, which tested expansion. confirmed ORR 0% evidence 6% 3) profile similar cohorts. 46% (6 13) non–small cell lung (NSCLC) cohort (median duration [DOR], NR) 28% 18) esophageal (EC) DOR, 15.2 [95% CI, 7.0 NR] months). Conclusions Relevance In this trial, well without atezolizumab; no new signals observed. Preliminary demonstrated regimen immunotherapy–naive metastatic NSCLC EC. Trial Registration ClinicalTrials.gov Identifier: NCT02794571

Language: Английский

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