Radiotherapy combined with immunotherapy: the dawn of cancer treatment

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

Published: July 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.

Language: Английский

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Applications of single-cell sequencing in cancer research: progress and perspectives

Journal of Hematology & Oncology, Journal Year: 2021, Volume and Issue: 14(1)

Published: June 9, 2021

Single-cell sequencing, including genomics, transcriptomics, epigenomics, proteomics and metabolomics is a powerful tool to decipher the cellular molecular landscape at single-cell resolution, unlike bulk which provides averaged data. The use of sequencing in cancer research has revolutionized our understanding biological characteristics dynamics within lesions. In this review, we summarize emerging technologies recent progress obtained by information related landscapes malignant cells immune cells, tumor heterogeneity, circulating underlying mechanisms behaviors. Overall, prospects facilitating diagnosis, targeted therapy prognostic prediction among spectrum tumors are bright. near future, advances will undoubtedly improve highlight potential precise therapeutic targets for patients.

Language: 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, Journal Year: 2020, Volume and Issue: 39(1), P. 30 - 37

Published: Aug. 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

Language: Английский

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Radiation therapy and anti-tumor immunity: exposing immunogenic mutations to the immune system

Genome Medicine, Journal Year: 2019, Volume and Issue: 11(1)

Published: June 20, 2019

The expression of antigens that are recognized by self-reactive T cells is essential for immune-mediated tumor rejection immune checkpoint blockade (ICB) therapy. Growing evidence suggests mutation-associated neoantigens drive ICB responses in tumors with high mutational burden. In most patients, only a few the mutations cancer exome predicted to be immunogenic cells. One factor limits this recognition level mutated gene product Substantial preclinical data show radiation can convert irradiated into site priming tumor-specific cells, is, an situ vaccine, and induce otherwise ICB-resistant tumors. Critical radiation-elicited T-cell activation induction viral mimicry, which mediated accumulation cytosolic DNA consequent cyclic GMP-AMP synthase (cGAS)/stimulator interferon (IFN) genes (STING) pathway downstream production type I IFN other pro-inflammatory cytokines. Recent suggest also enhance cell antigenicity upregulating large number involved response damage cellular stress, thus potentially exposing system. Here, we discuss how principles antigen presentation favor peptides derived from newly synthesized proteins These concepts support model incorporates presence upregulated predict patients might benefit treatment combinations radiotherapy ICB.

Language: Английский

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Pembrolizumab with or without radiation therapy for metastatic non-small cell lung cancer: a randomized phase I/II trial

Journal for ImmunoTherapy of Cancer, Journal Year: 2020, Volume and Issue: 8(2), P. e001001 - e001001

Published: Oct. 1, 2020

In this phase I/II trial, we evaluated the safety and effectiveness of pembrolizumab, with or without concurrent radiotherapy (RT), for lung liver lesions from metastatic non-small cell cancer (mNSCLC).Patients amenable to RT plus at least one additional non-contiguous lesion were included regardless programmed death-ligand 1 (PD-L1) status. Pembrolizumab was given 200 mg every 3 weeks up 32 cycles RT. Metastatic treated stereotactic body (SBRT; 50 Gy in 4 fractions) if clinically feasible traditionally fractionated (45 15 not. The primary end point best out-of-field response, a key secondary progression-free survival (PFS).The median follow-up time 20.4 months. One hundred patients (20 I, 80 II) evaluable toxicity, 72 II treatment response. No I group experienced grade 4-5 events; group, two had events nine events. ORR combined-modality cohort (irrespective schema) 22%, vs 25% pembrolizumab receipt salvage RT) (p=0.99). pembrolizumab+RT groups, ORRs 38% pembrolizumab+SBRT 10% pembrolizumab+traditional group. When examining pembrolizumab-alone patients, 33% those designated receive SBRT (if required) 17% traditional all PFS alone 5.1 months (95% CI 3.4 12.7 months), pembrolizumab/RT (regardless 9.1 3.6 18.4 months) (p=0.52). An exploratory analysis revealed that low PD-L1 expression, 4.6 20.8 RT, respectively (p=0.004).Concurrent immunoradiotherapy mNSCLC is safe, although larger trials are required address which benefit most RT.NCT02444741.

Language: Английский

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Overcoming Resistance to Tumor-Targeted and Immune-Targeted Therapies

Cancer Discovery, Journal Year: 2021, Volume and Issue: 11(4), P. 874 - 899

Published: April 1, 2021

Resistance to anticancer therapies includes primary resistance, usually related lack of target dependency or presence additional targets, and secondary mostly driven by adaptation the cancer cell selection pressure treatment. targeted therapy is frequently acquired, on-target, bypass alterations, cellular plasticity. immunotherapy often primary, orchestrated sophisticated tumor-host-microenvironment interactions, but could also occur after initial efficacy, when only partial responses are obtained. Here, we provide an overview resistance tumor immune-targeted discuss challenges overcoming current future directions development. SIGNIFICANCE: A better earlier identification cancer-resistance mechanisms avoid use ineffective drugs in patients not responding rationale for administration personalized drug associations. clear description molecular interplayers a prerequisite development novel dedicated drugs. Finally, implementation such immunologic explorations prospective clinical trials de-risk demonstration more effective strategies randomized registration trials, bring us closer promise cure.

Language: Английский

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Carbon Ion Radiobiology

Cancers, Journal Year: 2020, Volume and Issue: 12(10), P. 3022 - 3022

Published: Oct. 17, 2020

Radiotherapy using accelerated charged particles is rapidly growing worldwide. About 85% of the cancer patients receiving particle therapy are irradiated with protons, which have physical advantages compared to X-rays but a similar biological response. In addition ballistic advantages, heavy ions present specific radiobiological features that can make them attractive for treating radioresistant, hypoxic tumors. An ideal ion should lower toxicity in entrance channel (normal tissue) and be exquisitely effective target region (tumor). Carbon been chosen because they represent best combination this direction. Normal tissue toxicities second risk those observed conventional radiotherapy. region, increased relative effectiveness reduced oxygen enhancement ratio X-rays. Some properties densely ionizing carbon so distinct from protons considered as different “drug” oncology, may elicit favorable responses such an immune response angiogenesis metastatic potential. The guide patient selection treatment protocols achieve optimal clinical results.

Language: Английский

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Radiotherapy and Immunotherapy for Cancer: From “Systemic” to “Multisite”

Clinical Cancer Research, Journal Year: 2020, Volume and Issue: 26(12), P. 2777 - 2782

Published: Feb. 11, 2020

Abstract In the era of cancer immunotherapy, there is significant interest in combining conventional therapies, such as radiotherapy, with drugs that stimulate immune system. The observation ionizing radiation applied to murine tumors delays growth distant (“abscopal effect”) and this effect potentiated by immunostimulatory drugs, led clinical trials which often only one lesion irradiated combination immunotherapy drugs. results these initial radio therapy show a meaningful abscopal still infrequent. Recent preclinical data suggest preexistent intratumoral T cells can survive contribute its therapeutic effect. review, we discuss possible mechanisms underlying preclinical/clinical discrepancies regarding effect, propose irradiation multiple or all tumor sites systemic avenue increase efficacy radio-immunotherapy.

Language: Английский

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Addition of Metastasis-Directed Therapy to Intermittent Hormone Therapy for Oligometastatic Prostate Cancer

JAMA Oncology, Journal Year: 2023, Volume and Issue: 9(6), P. 825 - 825

Published: April 6, 2023

Despite evidence demonstrating an overall survival benefit with up-front hormone therapy in addition to established synergy between and radiation, the of metastasis-directed (MDT) for oligometastatic prostate cancer, date, has not been evaluated a randomized clinical trial.

Language: Английский

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Sequential transarterial chemoembolisation and stereotactic body radiotherapy followed by immunotherapy as conversion therapy for patients with locally advanced, unresectable hepatocellular carcinoma (START-FIT): a single-arm, phase 2 trial

˜The œLancet. Gastroenterology & hepatology, Journal Year: 2022, Volume and Issue: 8(2), P. 169 - 178

Published: Dec. 15, 2022

Language: Английский

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