Tertiary lymphoid structures and B cells determine clinically relevant T cell phenotypes in ovarian cancer DOI Creative Commons
Lenka Kašíková,

Jana Raková,

Michal Hensler

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 21, 2024

Abstract Intratumoral tertiary lymphoid structures (TLSs) have been associated with improved outcome in various cohorts of patients cancer, reflecting their contribution to the development tumor-targeting immunity. Here, we demonstrate that high-grade serous ovarian carcinoma (HGSOC) contains distinct immune aggregates varying degrees organization and maturation. Specifically, mature TLSs (mTLS) as forming only 16% HGSOCs relatively elevated tumor mutational burden (TMB) are an increased intratumoral density CD8 + effector T (T EFF ) cells TIM3 PD1 , hence poorly checkpoint inhibitor (ICI)-sensitive, cells. Conversely, from immunologically hot tumors like non-small cell lung (NSCLC) enriched ICI-responsive TCF1 Spatial B-cell profiling identifies patterns situ maturation differentiation mTLSs. Moreover, depletion promotes signs a dysfunctional compartment among tumor-infiltrating lymphocytes freshly isolated HGSOC NSCLC biopsies. Taken together, our data – at odds is low follicular helper thus develops limited number mTLS might be insufficient preserve ICI-sensitive phenotype. These findings point key quantitative qualitative differences between mTLSs vs ICI-irresponsive neoplasms may guide alternative immunotherapies for HGSOC.

Language: Английский

Myeloid-derived suppressor cells: an emerging target for anticancer immunotherapy DOI Creative Commons
Yuze Wu, Ming Yi,

Mengke Niu

et al.

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Sept. 26, 2022

Abstract The clinical responses observed following treatment with immune checkpoint inhibitors (ICIs) support immunotherapy as a potential anticancer treatment. However, large proportion of patients cannot benefit from it due to resistance or relapse, which is most likely attributable the multiple immunosuppressive cells in tumor microenvironment (TME). Myeloid-derived suppressor (MDSCs), heterogeneous array pathologically activated immature cells, are chief component networks. These potently suppress T-cell activity and thus contribute escape malignant tumors. New findings indicate that targeting MDSCs might be an alternative promising target for immunotherapy, reshaping enhancing efficacy cancer immunotherapy. In this review, we focus primarily on classification inhibitory function crosstalk between other myeloid cells. We also briefly summarize latest approaches therapies MDSCs.

Language: Английский

Citations

247
Role of tumor microenvironment in cancer progression and therapeutic strategy DOI Creative Commons
Qingjing Wang,

Xueting Shao,

Yuxuan Zhang

et al.

Cancer Medicine, Journal Year: 2023, Volume and Issue: 12(10), P. 11149 - 11165

Published: Feb. 21, 2023

Abstract Cancer is now considered a tumor microenvironment (TME) disease, although it was originally thought to be cell and gene expression disorder. Over the past 20 years, significant advances have been made in understanding complexity of TME its impact on responses various anticancer therapies, including immunotherapies. immunotherapy can recognize kill cancer cells by regulating body's immune system. It has achieved good therapeutic effects solid tumors hematological malignancies. Recently, blocking programmed death‐1 (PD‐1), ligand‐1 (PD‐L1), death Ligand‐2 (PD‐L2), construction antigen chimeric T (CAR‐T) vaccines become popular immunotherapies Tumorigenesis, progression, metastasis are closely related TME. Therefore, we review characteristics molecules TME, interaction between PD‐1 promising therapeutics.

Language: Английский

Citations

172
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
Durvalumab plus tremelimumab in advanced or metastatic soft tissue and bone sarcomas: a single-centre phase 2 trial DOI
Neeta Somaiah, Anthony P. Conley, Edwin R. Parra

et al.

The Lancet Oncology, Journal Year: 2022, Volume and Issue: 23(9), P. 1156 - 1166

Published: Aug. 4, 2022

Language: Английский

Citations

101
Chronic inflammation, cancer development and immunotherapy DOI Creative Commons

Yalei Wen,

Ying‐Jie Zhu, Caishi Zhang

et al.

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

Published: Oct. 14, 2022

Chronic inflammation plays a pivotal role in cancer development. Cancer cells interact with adjacent cellular components (pro-inflammatory cells, intrinsic immune stromal etc.) and non-cellular to form the inflammatory tumor microenvironment (TME). Interleukin 6 (IL-6), macrophage migration inhibitory factor (MIF), checkpoint factors other pro-inflammatory cytokines produced by TME are main mediators of intercellular communication TME, which link chronic stimulating different oncogenic signaling pathways improving escape promote In parallel, ability monocytes, T regulatory (Tregs) B (Bregs) perform homeostatic tolerogenic functions is hijacked leading local or systemic immunosuppression. Standard treatments for advanced malignancies such as chemotherapy radiotherapy have improved last decades. However, clinical outcomes certain malignant cancers not satisfactory due drug resistance side effects. The application therapy (ICT) has brought hope treatment, although therapeutic efficacy still limited immunosuppressive microenvironment. Emerging evidences reveal that ideal therapies including clearance disruption tumor-induced immunosuppression targeting suppressive well reactivation anti-tumor ICT. Here, we review impacts major their downstream molecules on We also discuss important management cancer.

Language: Английский

Citations

101
NK cells and solid tumors: therapeutic potential and persisting obstacles DOI Creative Commons
Le Tong, Carlos Jiménez‐Cortegana, Apple H.M. Tay

et al.

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Nov. 1, 2022

Abstract Natural killer (NK) cells, which are innate lymphocytes endowed with potent cytotoxic activity, have recently attracted attention as potential anticancer therapeutics. While NK cells mediate encouraging responses in patients leukemia, the therapeutic effects of cell infusion solid tumors limited. Preclinical and clinical data suggest that efficacy against malignancies is hampered by several factors including inadequate tumor infiltration persistence/activation microenvironment (TME). A number metabolic features TME hypoxia well elevated levels adenosine, reactive oxygen species, prostaglandins negatively affect activity. Moreover, cancer-associated fibroblasts, tumor-associated macrophages, myeloid-derived suppressor regulatory T actively suppress cell-dependent immunity. Here, we review cellular barriers inhibit neoplasms discuss strategies to circumvent such obstacles towards superior

Language: Английский

Citations

98
Hot and cold tumors: Immunological features and the therapeutic strategies DOI Creative Commons
Lianjie Wang, Hui Geng, Yujie Liu

et al.

MedComm, Journal Year: 2023, Volume and Issue: 4(5)

Published: Aug. 26, 2023

Abstract The “hotness” or “coldness” of the tumors are determined by information cancer cells themselves, tumor immune characteristics, microenvironment, and signaling mechanisms, which key factors affecting patients’ clinical efficacy. switch mechanism its corresponding pathological characteristics treatment strategies frontier hot spot treatment. How to distinguish effectively clarify causes, microenvironment state, very important for response efficacy treatments. Starting from concept cold tumor, this review systematically summarized molecular influencing factors, therapeutic “hot tumors,” analyzed immunophenotypes, pathways, markers that contribute tumors” in details. Different “cold based on were with drug targets proteins tumors.” Furthermore, combines different traditional medicine modern medicine, provide a basis guidance decision‐making

Language: Английский

Citations

97
Signaling pathways and targeted therapies in lung squamous cell carcinoma: mechanisms and clinical trials DOI Creative Commons

Zhenyi Niu,

Runsen Jin,

Yan Zhang

et al.

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

Published: Oct. 5, 2022

Lung cancer is the leading cause of cancer-related death across world. Unlike lung adenocarcinoma, patients with squamous cell carcinoma (LSCC) have not benefitted from targeted therapies. Although immunotherapy has significantly improved patients' outcomes, relatively low response rate and severe adverse events hinder clinical application this promising treatment in LSCC. Therefore, it vital importance to a better understanding mechanisms underlying pathogenesis LSCC as well inner connection among different signaling pathways, which will surely provide opportunities for more effective therapeutic interventions In review, new insights were given about classical pathways been proved other types but LSCC, including PI3K pathway, VEGF/VEGFR signaling, CDK4/6 pathway. Other may potentials also discussed, FGFR1 EGFR KEAP1/NRF2 Next, chromosome 3q, harbors two key differentiation markers SOX2 TP63 discussed its related potential targets. We provided some progress epigenetic therapies immune checkpoints blockade (ICB) Subsequently, we outlined combination strategies ICB Finally, prospects challenges exploration novel

Language: Английский

Citations

95
Immunotherapy: a promising approach for glioma treatment DOI Creative Commons
Feroza Yasinjan, Xing Yang,

Huayue Geng

et al.

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

Published: Sept. 7, 2023

Gliomas are the most prevalent primary malignant brain tumors worldwide, with glioblastoma (GBM) being common and aggressive type. Despite two decades of relentless pursuit in exploring novel therapeutic approaches for GBM, there is limited progress improving patients’ survival outcomes. Numerous obstacles impede effective treatment including immunosuppressive tumor microenvironment (TME), blood-brain barrier, extensive heterogeneity. these challenges, immunotherapies emerging as a promising avenue that may offer new hope gliomas. There four main types gliomas, immune checkpoint blockades, chimeric antigen receptor T-cell therapies, vaccines, oncolytic viruses. In addition, gene therapy, bispecific antibody combine therapy also briefly introduced this review. The significant role TME process has been emphasized many studies. Although immunotherapy enormous effort required to overcome existing barriers its success. Owing rapid development increasing attention paid article aims review recent advances

Language: Английский

Citations

84
Cardiovascular complications of immune checkpoint inhibitors for cancer DOI Open Access
Franck Thuny, Jarushka Naidoo, Tomas G. Neilan

et al.

European Heart Journal, Journal Year: 2022, Volume and Issue: 43(42), P. 4458 - 4468

Published: Aug. 30, 2022

Abstract Over the last decade or so, there has been a paradigm shift in oncologic care of patients with range solid tumour and haematologic malignancies, away from traditional cytotoxic chemotherapy towards personalized cancer treatments, using both targeted therapy immunotherapy. This contributed to remarkable sustained increase number survivors longevity diagnosis. review will focus on cardiovascular effects immune checkpoint inhibitors present background inhibition for cancer, epidemiology, potential mechanisms, insights into biology, diagnostic therapeutic approach cases. Our understanding needs improve. However, evolution necessarily be rapid. Initial observations noted that inhibitor can lead fulminant myocarditis. Recent reports have expanded effect system include an cardiac dysfunction without myocarditis, arrhythmias, venous thromboembolic disease, accelerated atherosclerosis, atherosclerosis-related events. The association between these events is not only limited occurring within first few weeks after starting but also occur months years therapy. latter observation especially relevance those treated adjuvant neoadjuvant There recognition currently approved therapies mechanisms adverse effects, who at risk, what we do about it.

Language: Английский

Citations

75