Molecular mechanisms of tumor resistance to radiotherapy

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

Published: June 15, 2023

Abstract Background Cancer is the most prevalent cause of death globally, and radiotherapy considered standard care for solid tumors, including lung, breast, esophageal, colorectal cancers glioblastoma. Resistance to radiation can lead local treatment failure even cancer recurrence. Main body In this review, we have extensively discussed several crucial aspects that resistance therapy, radiation-induced DNA damage repair, cell cycle arrest, apoptosis escape, abundance stem cells, modification cells their microenvironment, presence exosomal non-coding RNA, metabolic reprogramming, ferroptosis. We aim focus on molecular mechanisms in relation these discuss possible targets improve outcomes. Conclusions Studying responsible its interactions with tumor environment will help responses radiotherapy. Our review provides a foundation identify overcome obstacles effective

Language: Английский

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Radiotherapy and immunology

The Journal of Experimental Medicine, Journal Year: 2024, Volume and Issue: 221(7)

Published: May 21, 2024

The majority of cancer patients receive radiotherapy during the course treatment, delivered with curative intent for local tumor control or as part a multimodality regimen aimed at eliminating distant metastasis. A major focus research has been DNA damage; however, in past two decades, emphasis shifted to important role immune system plays radiotherapy-induced anti-tumor effects. Radiotherapy reprograms microenvironment, triggering and RNA sensing cascades that activate innate immunity ultimately enhance adaptive immunity. In opposition, also induces suppression immunity, including recruitment regulatory T cells, myeloid-derived suppressor suppressive macrophages. balance pro- is regulated by chemokines cytokines. Microbiota can influence outcomes under clinical investigation. Blockade PD-1/PD-L1 axis CTLA-4 extensively investigated combination radiotherapy; we include review trials involving inhibition these checkpoints radiotherapy.

Language: Английский

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Radiation-induced PD-L1 expression in tumor and its microenvironment facilitates cancer-immune escape: a narrative review

Annals of Translational Medicine, Journal Year: 2022, Volume and Issue: 10(24), P. 1406 - 1406

Published: Dec. 1, 2022

Background and Objective: Radiotherapy (RT) is one of the fundamental anti-cancer regimens by means inducing in situ tumor vaccination driving a systemic anti-tumor immune response. It can affect microenvironment (TME) components consisting blood vessels, immunocytes, fibroblasts, extracellular matrix (ECM), might subsequently suppress immunity through expression molecules such as programmed death ligand-1 (PD-L1). Immune checkpoint inhibitors (ICIs), especially anti-programmed cell 1 (PD-1)/PD-L1 therapies, have been regarded effective reinvigoration system another major cancer treatment. Experimentally, combination RT ICIs therapy shows greater synergistic effect than either alone. Methods: We performed narrative review literature PubMed database. The research string comprised various combinations "radiotherapy", "programmed death-ligand 1", "microenvironment", "exosome", "myeloid cell", "tumor immunity". database was searched independently two authors. A third reviewer mediated any discordance results screeners. Key Content Findings: upregulates PD-L1 cells, tumor-derived exosomes (TEXs), myeloid-derived suppressor cells (MDSCs), macrophages. signaling pathways correlated to include DNA damage pathway, epidermal growth factor receptor (EGFR) interferon gamma (IFN-γ) cGAS-STING JAK/STATs pathway. Conclusions: upregulation post-RT found not only but also TME mechanisms evasion. Therefore, further studies are necessary fully comprehend this biological process. Meanwhile, therapies has shown be effective, novel approaches developed adjuvant therapy.

Language: Английский

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Remodeling Tumor Immune Microenvironment by Using Polymer-Lipid-Manganese Dioxide Nanoparticles with Radiation Therapy to Boost Immune Response of Castration-Resistant Prostate Cancer

Research, Journal Year: 2023, Volume and Issue: 6

Published: Jan. 1, 2023

Despite substantial progress in the treatment of castration-resistant prostate cancer (CRPC), including radiation therapy and immunotherapy alone or combination, response to remains poor due hypoxic immunosuppressive nature tumor microenvironment. Herein, we exploited bioreactivity novel polymer–lipid manganese dioxide nanoparticles (PLMDs) remodel immune microenvironment (TIME) by increasing local oxygen levels extracellular pH enhancing radiation-induced immunogenic cell death. This study demonstrated that PLMD sensitized human murine CRPC cells radiation, significantly DNA double-strand breaks ultimately death, which enhanced secretion damage-associated molecular patterns, attributable induction autophagy endoplasmic reticulum stress. Reoxygenation via PLMDs also polarized RAW264.7 macrophages toward M1 phenotype, necrosis factor alpha release, thus reducing viability TRAMP-C2 cells. In a syngeneic model, intravenous injection suppressed, while recruitment regulatory T myeloid-derived suppressor Pretreatment with followed down-regulated programmed death-ligand 1 promoted infiltration antitumor CD8 + sites. Taken together, TIME modulation plus profoundly delayed growth prolonged median survival compared alone. These results suggest is promising modality for improving therapeutic efficacy radioresistant solid tumors.

Language: Английский

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CAR T cell-based immunotherapy and radiation therapy: potential, promises and risks

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

Published: May 12, 2023

Abstract CAR T cell-based therapies have revolutionized the treatment of hematological malignancies such as leukemia and lymphoma within last years. In contrast to success in cancers, solid tumors with cells is still a major challenge field attempts overcome these hurdles not been successful yet. Radiation therapy used for management various decades its therapeutic role ranges from local priming agent cancer immunotherapy. Combinations radiation immune checkpoint inhibitors already proven clinical trials. Therefore, combination may potential current limitations cell tumor entities. So far, only limited research was conducted area radiation. this review we will discuss risks patients.

Language: Английский

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Synergistic therapeutic strategies and engineered nanoparticles for anti-vascular endothelial growth factor therapy in cancer

Life Sciences, Journal Year: 2024, Volume and Issue: 341, P. 122499 - 122499

Published: Feb. 10, 2024

Language: Английский

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Cuproptosis, the novel type of oxidation-induced cell death in thoracic cancers: can it enhance the success of immunotherapy?

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: July 27, 2024

Abstract Copper is an important metal micronutrient, required for the balanced growth and normal physiological functions of human organism. Copper-related toxicity dysbalanced metabolism were associated with disruption intracellular respiration development various diseases, including cancer. Notably, copper-induced cell death was defined as cuproptosis which also observed in malignant cells, representing attractive anti-cancer instrument. Excess copper leads to aggregation lipoylation proteins toxic stress, ultimately resulting activation death. Differential expression cuproptosis-related genes detected tissues. Cuproptosis-related linked regulation oxidative immune responses, composition tumor microenvironment. Activation increased redox-metabolism-regulating genes, such ferredoxin 1 (FDX1), lipoic acid synthetase (LIAS), lipoyltransferase (LIPT1), dihydrolipoamide dehydrogenase (DLD), drolipoamide S-acetyltransferase (DLAT), pyruvate E1 subunit alpha (PDHA1), beta (PDHB)). Accordingly, copper-activated network suggested target cancer therapy. Mechanisms different cancers microenvironment are discussed this study. The analysis current findings indicates that therapeutic signaling, targets may provide effective tool improvement immunotherapy regimens. Graphical

Language: Английский

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Bladder-sparing strategies in patients with clinically localized muscle-invasive bladder cancer

Current Opinion in Urology, Journal Year: 2023, Volume and Issue: 33(5), P. 354 - 359

Published: June 30, 2023

Purpose of review Radical cystectomy is the standard care for patients with localized muscle-invasive bladder cancer (MIBC). In this context, bladder-sparing strategies (BSS) have been investigated as viable alternatives who are unfit radical or aim to preserve their without compromising oncological outcomes. This aims provide most up-to-date evidence on BSSs an alternative treatment MIBC. Recent findings Different studies highlighted long-term efficacy trimodal therapy chemoradiation protocols. However, due lack randomized controlled trials, there still a high-level BSS compared cystectomy. Consequently, adoption these approaches limited. A possible turning point could be represented by introduction immunotherapy, several investigating potential combination chemoradiotherapy radiotherapy alone. Patient selection, together implementation new predictive biomarkers and imaging tools, may improve in near future. Summary perioperative chemotherapy remains gold MIBC patients. Nevertheless, can considered option selected desire bladder. Further needed clearly state role

Language: Английский

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Prospects of Synergy: Local Interventions and CAR T Cell Therapy in Solid Tumors

BioDrugs, Journal Year: 2024, Volume and Issue: 38(5), P. 611 - 637

Published: July 30, 2024

Chimeric antigen receptor T cell therapy has been established in the treatment of various B malignancies. However, translating this therapeutic effect to treat solid tumors challenging because their inter-tumoral as well intratumoral heterogeneity and immunosuppressive microenvironment. Local interventions, such surgery, radiotherapy, local ablation, locoregional drug delivery, can enhance chimeric by improving tumor infiltration reducing systemic toxicities. Additionally, ablation radiotherapy have proven (re-)activate immune responses via abscopal effects reprogram microenvironment on a physical, cellular, chemical level. This review highlights potential synergy combined approaches overcome barriers summarizes recent studies that may pave way for new regimens.

Language: Английский

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Timing Anti-PD-L1 Checkpoint Blockade Immunotherapy to Enhance Tumor Irradiation

Cancers, Journal Year: 2025, Volume and Issue: 17(3), P. 391 - 391

Published: Jan. 24, 2025

Background: The ability of radiotherapy (RT) to drive anti-tumor immunity is limited by adaptive resistance. While RT induces inflammation and recruits activated tumor-infiltrating lymphocytes (TILs), including cytotoxic T (CTLs), the resulting radiation- IFNγ-dependent PD-L1 expression restores an immunosuppressed tumor microenvironment. Unleashing effective response may require precise sequencing checkpoint blockade immunotherapy (CBI) block signaling before it can mediate its suppressive effects. Methods: Flank tumors formed in BALB/c mice with syngeneic CT26 colon or 4T1 mammary carcinoma cells were treated otherwise ineffective doses ionizing radiation (10 Gy) followed CBI (0.2 mg anti-PD-L1, i.v.) after 0, 1, 3, 5, 7 days, comparing response. Anti-PD-L1 delivery was measured fluorescence, TILs flow cytometry immunofluorescence, immunohistochemistry, size calipers. Results: In both tumors, 10 Gy alone resulted a transient growth delay associated infiltrating CTLs peaking at 3 days 5 days. returned baseline consistent failed potentiate except when injected Gy, which prevented CTL depletion led elimination. Potentially contributing compound effects, anti-PD-L1 penetrated bound more efficiently irradiation. Conclusions: Optimal timing exploit radiation-induced permeability enhance interrupt resistance blocking as peaks offer general strategy external beam protecting potentiating immune

Language: Английский

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