Revisiting the role of CD4+ T cells in cancer immunotherapy—new insights into old paradigms

Cancer Gene Therapy, Год журнала: 2020, Номер 28(1-2), С. 5 - 17

Опубликована: Май 26, 2020

Cancer immunotherapy has revolutionised cancer treatment, with immune checkpoint blockade (ICB) therapy and adoptive cell (ACT) increasingly becoming standard of care across a growing number indications. While the majority immunotherapies focus on harnessing anti-tumour CD8+ cytotoxic T response, potential role CD4+ 'helper' cells largely remained in background. In this review, we give an overview multifaceted emphasis recent evidence that play bigger than previously thought. We illustrate their direct potency directing sustained response against tumours. further highlight emerging observation responses tumours tend to be self-derived epitopes. These trends raise vital questions considerations will profoundly affect rational design leverage full system cancer.

Язык: Английский

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Turning cold tumors into hot tumors by improving T-cell infiltration

Theranostics, Год журнала: 2021, Номер 11(11), С. 5365 - 5386

Опубликована: Янв. 1, 2021

Immunotherapy, represented by immune checkpoint inhibitors (ICIs), has greatly improved the clinical efficacy of malignant tumor therapy. ICI-mediated antitumor responses depend on infiltration T cells capable recognizing and killing cells. ICIs are not effective in "cold tumors", which characterized lack T-cell infiltration. To realize full potential immunotherapy solve this obstacle, it is essential to understand drivers into tumors. We present a critical review our understanding mechanisms underlying including impaired priming deficient homing beds. "Hot tumors" with significant associated better ICI efficacy. In review, we summarize multiple strategies that promote transformation "hot discuss these lead increased Finally, application nanomaterials provide an outlook future emerging field. The combination nanomedicines enhances cross-presentation antigens promotes A deeper opens new possibilities for development cell-based therapies improve effectiveness.

Язык: Английский

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Manganese Oxide Nanomaterials: Synthesis, Properties, and Theranostic Applications

Advanced Materials, Год журнала: 2020, Номер 32(10)

Опубликована: Янв. 28, 2020

Abstract Despite the comprehensive applications in bioimaging, biosensing, drug/gene delivery, and tumor therapy of manganese oxide nanomaterials (MONs including MnO 2 , MnO, Mn O 3 4 x ) their derivatives, a review article focusing on MON‐based nanoplatforms has not been reported yet. Herein, representative progresses MONs synthesis, heterogene, properties, surface modification, toxicity, imaging, biodetection, are mainly introduced. First, five kinds primary synthetic methods presented, thermal decomposition method, exfoliation strategy, permanganates reduction adsorption–oxidation hydro/solvothermal. Second, preparations hollow composite materials summarized specially. Then, chemical toxicity discussed. Next, diagnostic imaging sensing outlined. Finally, some rational designs photodynamic therapy, photothermal chemodynamic sonodynamic radiotherapy, magnetic hyperthermia, chemotherapy, gene starvation ferroptosis, immunotherapy, various combination highlighted.

Язык: Английский

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Challenges of combination therapy with immune checkpoint inhibitors for hepatocellular carcinoma

Journal of Hepatology, Год журнала: 2020, Номер 72(2), С. 307 - 319

Опубликована: Янв. 15, 2020

Язык: Английский

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Immunogenic Cell Death Activates the Tumor Immune Microenvironment to Boost the Immunotherapy Efficiency

Advanced Science, Год журнала: 2022, Номер 9(22)

Опубликована: Июнь 2, 2022

Abstract Tumor immunotherapy is only effective in a fraction of patients due to low response rate and severe side effects, these challenges clinics can be addressed through induction immunogenic cell death (ICD). ICD elicited from many antitumor therapies release danger associated molecular patterns (DAMPs) tumor‐associated antigens facilitate maturation dendritic cells (DCs) infiltration cytotoxic T lymphocytes (CTLs). The process reverse the tumor immunosuppressive microenvironment improve sensitivity immunotherapy. Nanostructure‐based drug delivery systems (NDDSs) are explored induce by incorporating therapeutic molecules for chemotherapy, photosensitizers (PSs) photodynamic therapy (PDT), photothermal conversion agents (PTT), radiosensitizers radiotherapy (RT). These NDDSs loaded at right dose place time, resulting greater effectiveness lower toxicity. Immunotherapeutic also combined with achieve synergic effect multi‐modality approach. In this review, harnessed load multiple PDT, PTT, RT combination promote reduce effects cancer treatment.

Язык: Английский

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Abscopal effect of radiotherapy combined with immune checkpoint inhibitors

Journal of Hematology & Oncology, Год журнала: 2018, Номер 11(1)

Опубликована: Авг. 16, 2018

Radiotherapy (RT) is used routinely as a standard treatment for more than 50% of patients with malignant tumors. The abscopal effect induced by local RT, which considered systemic anti-tumor immune response, reflects the regression non-irradiated metastatic lesions at distance from primary site irradiation. Since application immunotherapy, especially checkpoint inhibitors, can enhance response combination RT and immunotherapy has drawn extensive attention oncologists cancer researchers. Nevertheless, exact underlying mechanism remains unclear. In general, we speculate that responsible for, or least associated with, this effect. review, discuss blockade some published studies on type therapy. addition, also evaluate most appropriate time window blockade, well optimal dose fractionation in context combined treatment. Finally, significant purpose review to identify potential predictors help who would likely benefit modality.

Язык: Английский

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Radiotherapy combined with immunotherapy: the dawn of cancer treatment

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Июль 29, 2022

Abstract Radiotherapy (RT) is delivered for purposes of local control, but can also exert systemic effect on remote and non-irradiated tumor deposits, which called abscopal effect. The view RT as a simple treatment has dramatically changed in recent years, it now widely accepted that provoke immune response gives strong rationale the combination immunotherapy (iRT). Nevertheless, several points remain to be addressed such interaction system, identification best schedules with (IO), expansion mechanism amplify iRT. To answer these crucial questions, we roundly summarize underlying showing whole landscape clinical trials attempt identify In consideration rarity effect, propose occurrence induced by radiation promoted 100% molecular genetic level. Furthermore, “radscopal effect” refers using low-dose reprogram microenvironment may overcome resistance Taken together, could regarded trigger antitumor response, help IO used radical added into current standard regimen patients metastatic cancer.

Язык: Английский

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Dendritic Cell Paucity Leads to Dysfunctional Immune Surveillance in Pancreatic Cancer

Cancer Cell, Год журнала: 2020, Номер 37(3), С. 289 - 307.e9

Опубликована: Март 1, 2020

Язык: Английский

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Cell-Membrane Immunotherapy Based on Natural Killer Cell Membrane Coated Nanoparticles for the Effective Inhibition of Primary and Abscopal Tumor Growth

ACS Nano, Год журнала: 2018, Номер 12(12), С. 12096 - 12108

Опубликована: Ноя. 16, 2018

Developing effective immunotherapies with low toxicity and high tumor specificity is the ultimate goal in battle against cancer. Here, we reported a cell-membrane immunotherapy strategy that was able to eliminate primary tumors inhibited distant by using natural killer (NK) cell membrane cloaked photosensitizer 4,4',4'',4'''-(porphine-5,10,15,20-tetrayl) tetrakis (benzoic acid) (TCPP)-loaded nanoparticles (NK-NPs). The proteomic profiling of NK membranes performed through shotgun proteomics, found enabled NK-NPs target could induce or enhance pro-inflammatory M1-macrophages polarization produce antitumor immunity. TCPP loaded cancer death photodynamic therapy consequently enhanced immunity efficiency membranes. results confirmed selectively accumulated were growth an abscopal effect inhibit tumors. This immunotherapeutic approach offers for immunotherapy.

Язык: Английский

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Randomized Phase II Trial of Nivolumab With Stereotactic Body Radiotherapy Versus Nivolumab Alone in Metastatic Head and Neck Squamous Cell Carcinoma

Journal of Clinical Oncology, Год журнала: 2020, Номер 39(1), С. 30 - 37

Опубликована: Авг. 21, 2020

The objective response rate (ORR) for single-agent anti-programmed death receptor 1 (anti-PD-1) therapy is modest in patients with metastatic or recurrent head and neck squamous cell carcinoma (HNSCC). We aimed to test whether radiotherapy may act synergistically anti-PD-1 improve through the abscopal effect.We conducted a single-center, randomized, phase II trial of nivolumab (anti-PD-1 therapy) versus plus stereotactic body (SBRT) HNSCC. Patients had at least two lesions: one that could be safely irradiated measurable by RECIST version 1.1. were randomly assigned (1:1), stratified human papillomavirus status, (3 mg/kg intravenously every 2 weeks) (same dose) SBRT (9 Gy × 3) lesion. primary end point was ORR nonirradiated lesions, which assessed available set on-treatment images; safety per-protocol population.Between March 11, 2016, June 22, 2018, 62 (n = 30) 32). There no statistically significant difference between arms (34.5% [95% CI, 19.9% 52.7%] v 29.0% 16.1% 46.6%]; P .86). overall survival (P .75), progression-free .79), duration .26). Grade 3-5 toxicities similar (13.3% 9.7%; .70).We found improvement evidence an effect addition unselected

Язык: Английский

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