Suppressive immune microenvironment and CART therapy for glioblastoma: Future prospects and challenges DOI Creative Commons
Jie Lu,

Wen Huo,

Yingze Ma

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 600, P. 217185 - 217185

Published: Aug. 12, 2024

Glioblastoma, a highly malignant intracranial tumor, has acquired slow progress in treatment. Previous clinical trials involving targeted therapy and immune checkpoint inhibitors have shown no significant benefits treating glioblastoma. This ineffectiveness is largely due to the complex immunosuppressive environment of Glioblastoma cells exhibit low immunogenicity strong heterogeneity microenvironment replete with inhibitory cytokines, numerous cells, insufficient effective T cells. Fortunately, recent Phase I CART for glioblastoma confirmed its safety, small subset patients achieving survival benefits. However, continues face challenges, including blood-brain barrier obstruction, antigen loss, an tumor (TME). article provides detailed examination glioblastoma's microenvironment, both from intrinsic extrinsic cell factors, reviews current basic research on multi-targets treatment, concludes by outlining key challenges using therapy.

Language: Английский

Artificial intelligence in neuro-oncology: advances and challenges in brain tumor diagnosis, prognosis, and precision treatment DOI Creative Commons
Sirvan Khalighi, Kartik Reddy, Abhishek Midya

et al.

npj Precision Oncology, Journal Year: 2024, Volume and Issue: 8(1)

Published: March 29, 2024

Abstract This review delves into the most recent advancements in applying artificial intelligence (AI) within neuro-oncology, specifically emphasizing work on gliomas, a class of brain tumors that represent significant global health issue. AI has brought transformative innovations to tumor management, utilizing imaging, histopathological, and genomic tools for efficient detection, categorization, outcome prediction, treatment planning. Assessing its influence across all facets malignant management- diagnosis, prognosis, therapy- models outperform human evaluations terms accuracy specificity. Their ability discern molecular aspects from imaging may reduce reliance invasive diagnostics accelerate time diagnoses. The covers techniques, classical machine learning deep learning, highlighting current applications challenges. Promising directions future research include multimodal data integration, generative AI, large medical language models, precise delineation characterization, addressing racial gender disparities. Adaptive personalized strategies are also emphasized optimizing clinical outcomes. Ethical, legal, social implications discussed, advocating transparency fairness integration neuro-oncology providing holistic understanding impact patient care.

Language: Английский

Citations

53
Current challenges and therapeutic advances of CAR-T cell therapy for solid tumors DOI Creative Commons
T. R. Chen, Mingzhao Wang, Yanchao Chen

et al.

Cancer Cell International, Journal Year: 2024, Volume and Issue: 24(1)

Published: April 15, 2024

Abstract The application of chimeric antigen receptor (CAR) T cells in the management hematological malignancies has emerged as a noteworthy therapeutic breakthrough. Nevertheless, utilization and effectiveness CAR-T cell therapy solid tumors are still limited primarily because absence tumor-specific target antigen, existence immunosuppressive tumor microenvironment, restricted invasion proliferation, occurrence severe toxicity. This review explored history its latest advancements tumors. According to recent studies, optimizing design cells, implementing logic-gated refining delivery methods agents can all enhance efficacy therapy. Furthermore, combination shows promise way improve At present, numerous clinical trials involving for actively progress. In conclusion, both potential challenges when it comes treating As continues evolve, further innovations will be devised surmount associated with this treatment modality, ultimately leading enhanced response patients suffered

Language: Английский

Citations

32
Navigating tumor angiogenesis: therapeutic perspectives and myeloid cell regulation mechanism DOI Creative Commons
Fan Yang,

Gloria Lee,

Yi Fan

et al.

Angiogenesis, Journal Year: 2024, Volume and Issue: 27(3), P. 333 - 349

Published: April 6, 2024

Abstract Sustained angiogenesis stands as a hallmark of cancer. The intricate vascular tumor microenvironment fuels cancer progression and metastasis, fosters therapy resistance, facilitates immune evasion. Therapeutic strategies targeting vasculature have emerged transformative for treatment, encompassing anti-angiogenesis, vessel normalization, endothelial reprogramming. Growing evidence suggests the dynamic regulation by infiltrating myeloid cells, such macrophages, myeloid-derived suppressor cells (MDSCs), neutrophils. Understanding these regulatory mechanisms is pivotal in paving way successful vasculature-targeted treatments. interventions aimed to disrupt cell-mediated may reshape overcome resistance radio/chemotherapy immunotherapy.

Language: Английский

Citations

21
Multiphoton fluorescence microscopy for in vivo imaging DOI
Chris Xu, Maiken Nedergaard, Deborah J. Fowell

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(17), P. 4458 - 4487

Published: Aug. 1, 2024

Language: Английский

Citations

21
The dilemmas and possible solutions for CAR-T cell therapy application in solid tumors DOI Creative Commons
Lihong Wang, Lufang Zhang,

Louisa Chard Dunmall

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 591, P. 216871 - 216871

Published: April 10, 2024

Chimeric antigen receptor T (CAR-T) cell therapy, as an adoptive immunotherapy, is playing increasingly important role in the treatment of malignant tumors. CAR-T cells are referred to "living drugs" they not only target tumor directly, but also induce long-term immune memory that has potential provide long-lasting protection. CD19.CAR-T have achieved complete response rates over 90% for acute lymphoblastic leukemia and 60% non-Hodgkin's lymphoma. However, rate solid tumors remains extremely low side effects potentially severe. In this review, we discuss limitations microenvironment poses application solutions being developed address these limitations, hope near future, therapy can attain same success now seen clinically hematological malignancies.

Language: Английский

Citations

18
The peritumor microenvironment: physics and immunity DOI Creative Commons
Sue Zhang, Kathryn Regan, Julian Najera

et al.

Trends in cancer, Journal Year: 2023, Volume and Issue: 9(8), P. 609 - 623

Published: May 6, 2023

Language: Английский

Citations

26
The Complex Tumor Microenvironment in Ovarian Cancer: Therapeutic Challenges and Opportunities DOI Creative Commons
Bianca Garlisi,

Sylvia Lauks,

Caroline Aitken

et al.

Current Oncology, Journal Year: 2024, Volume and Issue: 31(7), P. 3826 - 3844

Published: July 1, 2024

The tumor microenvironment (TME) in ovarian cancer (OC) has much greater complexity than previously understood. In response to aggressive pro-angiogenic stimulus, blood vessels form rapidly and are dysfunctional, resulting poor perfusion, tissue hypoxia, leakiness, which leads increased interstitial fluid pressure (IFP). Decreased perfusion high IFP significantly inhibit the uptake of therapies into tumor. Within TME, there numerous inhibitor cells, such as myeloid-derived suppressor cells (MDSCs), association macrophages (TAMs), regulatory T (Tregs), cancer-associated fibroblasts (CAFs) that secrete numbers immunosuppressive cytokines. This environment is thought contribute lack success immunotherapies immune checkpoint (ICI) treatment. review discusses components TME OC, how these characteristics impede therapeutic efficacy, some strategies alleviate this inhibition.

Language: Английский

Citations

13
Chimeric Antigen Receptor T Cells in Glioblastoma—Current Concepts and Promising Future DOI Creative Commons

Rebecca Kringel,

Katrin Lamszus, Malte Mohme

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(13), P. 1770 - 1770

Published: July 3, 2023

Glioblastoma (GBM) is a highly aggressive primary brain tumor that largely refractory to treatment and, therefore, invariably relapses. GBM patients have median overall survival of 15 months given this devastating prognosis, there high need for therapy improvement. One the therapeutic approaches currently tested in chimeric antigen receptor (CAR)-T cell therapy. CAR-T cells are genetically altered T redirected eliminate specific manner. There several challenges solid tumors such as GBM, including restricted trafficking and penetration tissue, immunosuppressive microenvironment (TME), well heterogeneous expression loss. In addition, limitations concerning safety, toxicity, manufacturing process. To date, directed against target antigens interleukin-13 alpha 2 (IL-13Rα2), epidermal growth factor variant III (EGFRvIII), human (HER2), ephrin type-A (EphA2) been preclinical clinical studies. These studies demonstrated feasible option with at least transient responses acceptable adverse effects. Further improvements regarding their efficacy, flexibility, safety could render them promising GBM.

Language: Английский

Citations

17
Biophysical and biochemical aspects of immune cell–tumor microenvironment interactions DOI Creative Commons

Shoham Benmelech,

Thien Le,

M. McKay

et al.

APL Bioengineering, Journal Year: 2024, Volume and Issue: 8(2)

Published: April 2, 2024

The tumor microenvironment (TME), composed of and influenced by a heterogeneous set cancer cells an extracellular matrix, plays crucial role in progression. biophysical aspects the TME (namely, its architecture mechanics) regulate interactions spatial distributions immune cells. In this review, we discuss factors TME—notably, as well stromal cells—that contribute to pro-tumor, immunosuppressive response. We then ways which innate adaptive systems respond tumors from both biochemical perspectives, with increased focus on CD8+ CD4+ T Building upon information, turn immune-based antitumor interventions—specifically, recent breakthroughs aimed at improving CAR-T cell therapy.

Language: Английский

Citations

7
Normalizing granuloma vasculature and matrix improves drug delivery and reduces bacterial burden in tuberculosis-infected rabbits DOI Creative Commons
Meenal Datta, Laura E. Via, Véronique Dartois

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(14)

Published: March 26, 2024

Host-directed therapies (HDTs) represent an emerging approach for bacterial clearance during tuberculosis (TB) infection. While most HDTs are designed and implemented immuno-modulation, other host targets-such as nonimmune stromal components found in pulmonary granulomas-may prove equally viable. Building on our previous work characterizing normalizing the aberrant granuloma-associated vasculature, here we demonstrate that FDA-approved (bevacizumab losartan, respectively) can be repurposed to normalize blood vessels extracellular matrix (ECM), improve drug delivery, reduce loads TB granulomas. Granulomas feature overabundance of ECM compressed vessels, both which effectively reduced by losartan treatment rabbit model TB. Combining promotes secretion proinflammatory cytokines improves anti-TB delivery. Finally, alone combination with second-line antitubercular agents (moxifloxacin or bedaquiline), these significantly burden. RNA sequencing analysis HDT-treated lung granuloma tissues implicates up-regulated antimicrobial peptide gene expression ciliated epithelial airway cells a putative mechanism observed benefits absence chemotherapy. These findings bevacizumab well-tolerated stroma-targeting HDTs, microenvironment, outcomes, providing rationale clinically test this patients.

Language: Английский

Citations

6