Mechanisms of drug resistance to immune checkpoint inhibitors in non-small cell lung cancer DOI Creative Commons
Kexun Zhou, Shuo Li, Yi Zhao

et al.

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

Published: Feb. 8, 2023

Immune checkpoint inhibitors (ICIs) in the form of anti-CTLA-4 and anti-PD-1/PD-L1 have become frontier cancer treatment successfully prolonged survival patients with advanced non-small cell lung (NSCLC). But efficacy varies among different patient population, many succumb to disease progression after an initial response ICIs. Current research highlights heterogeneity resistance mechanisms critical role tumor microenvironment (TME) ICIs resistance. In this review, we discussed NSCLC, proposed strategies overcome

Language: Английский

Tiragolumab plus atezolizumab versus placebo plus atezolizumab as a first-line treatment for PD-L1-selected non-small-cell lung cancer (CITYSCAPE): primary and follow-up analyses of a randomised, double-blind, phase 2 study DOI
Byoung Chul Cho, Delvys Rodríguez‐Abreu, Maen Hussein

et al.

The Lancet Oncology, Journal Year: 2022, Volume and Issue: 23(6), P. 781 - 792

Published: May 13, 2022

Language: Английский

Citations

287
Immunotherapy in Lung Cancer: Current Landscape and Future Directions DOI Creative Commons
Hirva Mamdani, Sandro Matosevic,

Ahmed Bilal Khalid

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Feb. 9, 2022

Over the past decade, lung cancer treatment has undergone a major paradigm shift. A greater understanding of biology led to development many effective targeted therapies as well immunotherapy. Immune checkpoint inhibitors (ICIs) have shown tremendous benefit in non-small cell (NSCLC) and are now being used first-line metastatic disease, consolidation therapy following chemoradiation unresectable locally advanced adjuvant surgical resection chemotherapy resectable disease. Despite these benefits, predicting who will respond ICIs proven be difficult there remains need discover new predictive immunotherapy biomarkers. Furthermore, resistance is frequent either because lack response or disease progression after an initial response. The utility small (SCLC) limited extensive stage combination with modest impact on overall survival. It thus important explore exploit additional targets reap full benefits cancer. Here, we summarize current state cancer, discuss novel targets, intersection between DNA repair defects

Language: Английский

Citations

227
Cancer immunotherapies: advances and bottlenecks DOI Creative Commons
Rui Rui, Liqun Zhou, Shiming He

et al.

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

Citations

176
Targeting LAG-3, TIM-3, and TIGIT for cancer immunotherapy DOI Creative Commons
Letong Cai, Yuchen Li, Jiaxiong Tan

et al.

Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)

Published: Sept. 5, 2023

Abstract In one decade, immunotherapy based on immune checkpoint blockades (ICBs) has become a new pillar of cancer treatment following surgery, radiation, chemotherapy, and targeted therapies. However, not all patients benefit from single or combination therapy with anti-CTLA-4 anti-PD-1/PD-L1 monoclonal antibodies. Thus, an increasing number proteins (ICPs) have been screened their effectiveness evaluated in preclinical clinical trials. Lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin mucin-domain-containing-3 (TIM-3), immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) constitute the second wave targets that show great promise for use solid tumors leukemia. To promote research application ICBs directed at these targets, we summarize discovery, mechanism, efficiency, trial results this review.

Language: Английский

Citations

129
TIGIT-CD226-PVR axis: advancing immune checkpoint blockade for cancer immunotherapy DOI Creative Commons
Eugene Y. Chiang, Ira Mellman

Journal for ImmunoTherapy of Cancer, Journal Year: 2022, Volume and Issue: 10(4), P. e004711 - e004711

Published: April 1, 2022

Recent advances in understanding the roles of immune checkpoints allowing tumors to circumvent system have led successful therapeutic strategies that fundamentally changed oncology practice. Thus far, immunotherapies against only two checkpoint targets been approved, CTLA-4 and PD-L1/PD-1. Antibody blockade these enhances function antitumor T cells at least part by relieving inhibition cell costimulatory receptor CD28. These successes stimulated considerable interest identifying other pathways may bte targeted alone or together with existing immunotherapies. One such axis is comprised members PVR/nectin family includes inhibitory immunoreceptor Ig tyrosine-based domains (TIGIT). Interestingly, TIGIT acts regulate activity a second CD226 works parallel There are currently over dozen TIGIT-directed blocking antibodies various phases clinical development, testament promise modulating this pathway enhance responses. In review, we discuss role as inhibitor, its interplay activating counter-receptor CD226, status next advance cancer immunotherapy.

Language: Английский

Citations

124
Anti-TIGIT therapies for solid tumors: a systematic review DOI Creative Commons

A. Rousseau,

Claudia Parisi, Fabrice Barlési

et al.

ESMO Open, Journal Year: 2023, Volume and Issue: 8(2), P. 101184 - 101184

Published: March 16, 2023

•Anti-TIGIT antibodies are a new therapy in solid tumors.•In vitro models showed that TIGIT inhibition could restore antitumor response.•The ClinicalTrials.gov database references 70 trials of anti-TIGIT patients with cancer.•This paper provides comprehensive review about ongoing and biological background therapies. Programmed death-ligand 1[PD-(L)1], cytotoxic T-lymphocyte associated protein 4 (CTLA-4), lymphocyte-activation gene 3 (LAG-3) inhibitors recent breakthroughs cancer treatment, however not all benefit from it. Thus therapies under investigation, such as [anti-T-cell immunoreceptor immunoglobulin (Ig) tyrosine-based inhibitory motif domains] antibodies. is an immune checkpoint inhibiting lymphocyte T cells by several mechanisms. In its response. Furthermore, association anti-PD-(L)1 synergistically improve survival. We carried out the clinical trial referenced PubMed database, finding three published on Vibostolimab was evaluated phase I alone or combination pembrolizumab. The had objective response rate 26% non-small-cell lung (NSCLC) naïve anti-programmed cell death 1 (anti-PD-1). Etigilimab tested nivolumab, but study stopped due to business reasons. II CITYSCAPE trial, tiragolumab demonstrated higher progression-free survival atezolizumab than advanced PD-L1-high NSCLC. cancer, 47 them recruitment. Only seven were III, including five NSCLC, mostly therapy. Data I-II highlighted targeting represents safe therapeutic approach, acceptable toxicity profile maintained when adding Frequent adverse events pruritus, rash, fatigue. Grade 3-4 reported nearly one patients. Anti-TIGIT development novel immunotherapy approach. A promising research area includes anti-PD-1 NSCLCs.

Language: Английский

Citations

90
Co-inhibition of TIGIT and PD-1/PD-L1 in Cancer Immunotherapy: Mechanisms and Clinical Trials DOI Creative Commons

Xianjing Chu,

Wentao Tian, Ziqi Wang

et al.

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

Citations

90
At the crossroads of immunotherapy for oncogene-addicted subsets of NSCLC DOI
Itziar Otano, Álvaro C. Ucero, Jon Zugazagoitia

et al.

Nature Reviews Clinical Oncology, Journal Year: 2023, Volume and Issue: 20(3), P. 143 - 159

Published: Jan. 13, 2023

Language: Английский

Citations

84
Exploiting innate immunity for cancer immunotherapy DOI Creative Commons
Ming Yi, Tianye Li,

Mengke Niu

et al.

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

Published: Nov. 27, 2023

Abstract Immunotherapies have revolutionized the treatment paradigms of various types cancers. However, most these immunomodulatory strategies focus on harnessing adaptive immunity, mainly by inhibiting immunosuppressive signaling with immune checkpoint blockade, or enhancing immunostimulatory bispecific T cell engager and chimeric antigen receptor (CAR)-T cell. Although agents already achieved great success, only a tiny percentage patients could benefit from immunotherapies. Actually, immunotherapy efficacy is determined multiple components in tumor microenvironment beyond immunity. Cells innate arm system, such as macrophages, dendritic cells, myeloid-derived suppressor neutrophils, natural killer unconventional also participate cancer evasion surveillance. Considering that cornerstone antitumor response, utilizing immunity provides potential therapeutic options for control. Up to now, exploiting agonists stimulator interferon genes, CAR-macrophage -natural therapies, metabolic regulators, novel exhibited potent activities preclinical clinical studies. Here, we summarize latest insights into roles cells discuss advances arm-targeted strategies.

Language: Английский

Citations

84
Recent Advances and Challenges in Cancer Immunotherapy DOI Open Access

Chelsea Peterson,

Nathan Denlinger, Yiping Yang

et al.

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

Citations

81