Interferon-stimulated neutrophils as a predictor of immunotherapy response

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(2), P. 253 - 265.e12

Published: Jan. 4, 2024

Despite the remarkable success of anti-cancer immunotherapy, its effectiveness remains confined to a subset patients—emphasizing importance predictive biomarkers in clinical decision-making and further mechanistic understanding treatment response. Current biomarkers, however, lack power required accurately stratify patients. Here, we identify interferon-stimulated, Ly6Ehi neutrophils as blood-borne biomarker anti-PD1 response mice at baseline. are induced by tumor-intrinsic activation STING (stimulator interferon genes) signaling pathway possess ability directly sensitize otherwise non-responsive tumors therapy, part through IL12b-dependent cytotoxic T cells. By translating our pre-clinical findings cohort patients with non-small cell lung cancer melanoma (n = 109), public data 1440), demonstrate predict immunotherapy humans high accuracy (average AUC ≈ 0.9). Overall, study identifies functionally active for use both humans.

Language: Английский

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Application of radiomics-based multiomics combinations in the tumor microenvironment and cancer prognosis

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: Sept. 6, 2023

Abstract The advent of immunotherapy, a groundbreaking advancement in cancer treatment, has given rise to the prominence tumor microenvironment (TME) as critical area research. clinical implications an improved understanding TME are significant and far-reaching. Radiomics been increasingly utilized comprehensive assessment prognosis. Similarly, pathomics, which is based on pathological images, can offer additional insights into panoramic view microscopic information tumors. combination pathomics radiomics revolutionized concept “digital biopsy”. As genomics transcriptomics continue evolve, integrating with genomic transcriptomic datasets further heterogeneity establish correlations biological significance. Therefore, synergistic analysis digital image features (radiomics, pathomics) genetic phenotypes (genomics) comprehensively decode characterize well predict This review presents summary research important biomarkers for predicting TME, emphasizing interplay between radiomics, genomics, transcriptomics, application multiomics decoding Finally, we discuss challenges opportunities In conclusion, this highlights crucial role associations combined promising direction substantial significance value evaluation prognosis assessment.

Language: Английский

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Current and future immunotherapeutic approaches in pancreatic cancer treatment

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

Published: June 4, 2024

Abstract Pancreatic cancer is a major cause of cancer-related death, but despondently, the outlook and prognosis for this resistant type tumor have remained grim long time. Currently, it extremely challenging to prevent or detect early enough effective treatment because patients rarely exhibit symptoms there are no reliable indicators detection. Most advanced spreading that difficult treat, treatments like chemotherapy radiotherapy can only slightly prolong their life by few months. Immunotherapy has revolutionized pancreatic cancer, yet its effectiveness limited tumor's immunosuppressive hard-to-reach microenvironment. First, article explains microenvironment highlights wide range immunotherapy options, including therapies involving oncolytic viruses, modified T cells (T-cell receptor [TCR]-engineered chimeric antigen [CAR] T-cell therapy), CAR natural killer cell therapy, cytokine-induced cells, immune checkpoint inhibitors, immunomodulators, vaccines, strategies targeting myeloid in context contemporary knowledge future trends. Lastly, discusses main challenges ahead immunotherapy.

Language: Английский

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Deep learning in cancer genomics and histopathology

Genome Medicine, Journal Year: 2024, Volume and Issue: 16(1)

Published: March 27, 2024

Abstract Histopathology and genomic profiling are cornerstones of precision oncology routinely obtained for patients with cancer. Traditionally, histopathology slides manually reviewed by highly trained pathologists. Genomic data, on the other hand, is evaluated engineered computational pipelines. In both applications, advent modern artificial intelligence methods, specifically machine learning (ML) deep (DL), have opened up a fundamentally new way extracting actionable insights from raw which could augment potentially replace some aspects traditional evaluation workflows. this review, we summarize current emerging applications DL in genomics, including basic diagnostic as well advanced prognostic tasks. Based growing body evidence, suggest that be groundwork kind workflow cancer research. However, also point out models can biases flaws users healthcare research need to know about, propose ways address them.

Language: Английский

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Cellular interactions in tumor microenvironment during breast cancer progression: new frontiers and implications for novel therapeutics

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: March 12, 2024

The breast cancer tumor microenvironment (TME) is dynamic, with various immune and non-immune cells interacting to regulate progression anti-tumor immunity. It now evident that the within TME significantly contribute resistance conventional newly developed therapies. Both in play critical roles onset, uncontrolled proliferation, metastasis, evasion, Consequently, molecular cellular components of have emerged as promising therapeutic targets for developing novel treatments. primarily comprises cells, stromal vasculature, infiltrating cells. Currently, numerous clinical trials targeting specific are underway. However, complexity its impact on evasion immunity necessitate further research develop improved multifaceted nature arises from their phenotypic functional plasticity, which endows them both pro during progression. In this review, we discuss current understanding recent advances anti-tumoral functions implications safe effective therapies control progress.

Language: Английский

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Present and future of cancer nano-immunotherapy: opportunities, obstacles and challenges

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 18, 2025

Clinically, multimodal therapies are adopted worldwide for the management of cancer, which continues to be a leading cause death. In recent years, immunotherapy has firmly established itself as new paradigm in cancer care that activates body's immune defense cope with cancer. Immunotherapy resulted significant breakthroughs treatment stubborn tumors, dramatically improving clinical outcome patients. Multiple forms immunotherapy, including checkpoint inhibitors (ICIs), adoptive cell therapy and vaccines, have become widely available. However, effectiveness these immunotherapies is not much satisfying. Many patients do respond disease recurrence appears unavoidable because rapidly evolving resistance. Moreover, can give rise severe off-target immune-related adverse events. Strategies remove hindrances mainly focus on development combinatorial or exploitation novel immunotherapeutic mediations. Nanomaterials carrying anticancer agents target site considered practical approaches treatment. Nanomedicine combined offers possibility potentiate systemic antitumor immunity facilitate selective cytotoxicity against cells an effective safe manner. A myriad nano-enabled currently under investigation. Owing gaps between preclinical studies, nano-immunotherapy faces multiple challenges, biosafety nanomaterials trial design. this review, we provide overview summarize evidence indicating how nanomedicine-based increase efficacy immunotherapies. We also discuss key challenges emerged era nanotechnology-based immunotherapy. Taken together, combination drawing increasing attention, it anticipated will achieve desired success therapy.

Language: Английский

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Biological and clinical significance of tumour-infiltrating lymphocytes in the era of immunotherapy: a multidimensional approach

Nature Reviews Clinical Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 16, 2025

Language: Английский

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Clinical Advances and Perspectives in Targeted Radionuclide Therapy

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(6), P. 1733 - 1733

Published: June 14, 2023

Targeted radionuclide therapy has become increasingly prominent as a nuclear medicine subspecialty. For many decades, treatment with radionuclides been mainly restricted to the use of iodine-131 in thyroid disorders. Currently, radiopharmaceuticals, consisting coupled vector that binds desired biological target high specificity, are being developed. The objective is be selective possible at tumor level, while limiting dose received healthy tissue level. In recent years, better understanding molecular mechanisms cancer, well appearance innovative targeting agents (antibodies, peptides, and small molecules) availability new radioisotopes, have enabled considerable advances field vectorized internal radiotherapy therapeutic efficacy, radiation safety personalized treatments. instance, microenvironment, instead cancer cells, now appears particularly attractive. Several radiopharmaceuticals for shown clinical value several types tumors or will soon approved authorized use. Following their commercial success, research domain growing, pipeline appearing promising target. This review aims provide an overview current on therapy.

Language: Английский

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Building a Better Defense: Expanding and Improving Natural Killer Cells for Adoptive Cell Therapy

Cells, Journal Year: 2024, Volume and Issue: 13(5), P. 451 - 451

Published: March 5, 2024

Natural killer (NK) cells have gained attention as a promising adoptive cell therapy platform for their potential to improve cancer treatments. NK offer distinct advantages over T-cells, including major histocompatibility complex class I (MHC-I)-independent tumor recognition and low risk of toxicity, even in an allogeneic setting. Despite this tremendous potential, challenges persist, such limited vivo persistence, reduced infiltration, absolute numbers. This review outlines several strategies aiming overcome these challenges. The developed include optimizing expansion methods improving antitumor responses by cytokine stimulation genetic manipulations. Using K562 expressing membrane IL-15 or IL-21 with without additional activating ligands like 4-1BBL allows “massive” makes multiple dosing “off-the-shelf” efforts feasible. Further improvements function can be reached inducing memory-like cells, developing chimeric antigen receptor (CAR)-NK isolating NK-cell-based tumor-infiltrating lymphocytes (TILs). Memory-like demonstrate higher persistence cytotoxicity, early clinical trials demonstrating safety efficacy. Recent using CAR-NK also demonstrated lack any release syndrome, and, yet, activity. data support that the presence TIL-NK is associated improved overall patient survival different types solid tumors head neck, colorectal, breast, gastric carcinomas, among most significant. In conclusion, presents insights into diverse available expansion, roles played various cytokines, feeder culture material influencing activation phenotype, telomere length, cytotoxic expanded cells. Notably, genetically modified significant efficacy promoting expansion. Furthermore, culturing IL-2 has been shown rates, while IL-12 linked enhanced function. Overall, provides overview methodologies, highlighting current landscape key advancements enhance therapy.

Language: Английский

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Biomarker discovery in hepatocellular carcinoma (HCC) for personalized treatment and enhanced prognosis

Cytokine & Growth Factor Reviews, Journal Year: 2024, Volume and Issue: 79, P. 29 - 38

Published: Aug. 24, 2024

Language: Английский

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