Mechanisms of radiotherapy resistance and radiosensitization strategies for esophageal squamous cell carcinoma

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

Published: Aug. 19, 2023

Abstract Esophageal squamous cell carcinoma (ESCC) is the sixth most common cause of cancer-related mortality worldwide, with more than half them occurred in China. Radiotherapy (RT) has been widely used for treating ESCC. However, radiation-induced DNA damage response (DDR) can promote release cytokines and chemokines, triggers inflammatory reactions changes tumor microenvironment (TME), thereby inhibiting immune function causing invasion metastasis Radioresistance major disease progression cancer, it associated heterogeneity. Therefore, a better understanding radioresistance mechanisms may generate reversal strategies to improve cure rates survival periods ESCC patients. We mainly summarized possible order reveal new targets therapy. Then we compared current reverse radioresistance.

Language: Английский

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Progenitor-like exhausted SPRY1+CD8+ T cells potentiate responsiveness to neoadjuvant PD-1 blockade in esophageal squamous cell carcinoma

Cancer Cell, Journal Year: 2023, Volume and Issue: 41(11), P. 1852 - 1870.e9

Published: Oct. 12, 2023

Neoadjuvant immune checkpoint blockade (ICB) demonstrates promise in operable esophageal squamous cell carcinoma (ESCC), but lacks available efficacy biomarkers. Here, we perform single-cell RNA-sequencing of tumors from patients with ESCC undergoing neoadjuvant ICB, revealing a subset exhausted CD8+ T cells expressing SPRY1 (CD8+ Tex-SPRY1) that displays progenitor (Tpex) phenotype and correlates complete response to ICB. We validate Tex-SPRY1 as an ICB-specific predictor improved survival using independent ICB-/non-ICB cohorts demonstrate expression enforces Tpex enhances ICB efficacy. Additionally, contribute proinflammatory macrophages functional state B cells, which thereby promotes antitumor immunity by enhancing effector functions. Overall, our findings unravel progenitor-like cells' role effective responses for inform mechanistic biomarkers future individualized immunotherapy.

Language: Английский

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Advances in diagnosis and management of cancer of the esophagus

BMJ, Journal Year: 2024, Volume and Issue: unknown, P. e074962 - e074962

Published: June 3, 2024

Abstract Esophageal cancer is the seventh most common malignancy worldwide, with over 470 000 new cases diagnosed each year. Two distinct histological subtypes predominate, and should be considered biologically separate disease entities.1 These are esophageal adenocarcinoma (EAC) squamous cell carcinoma (ESCC). Outcomes remain poor regardless of subtype, patients presenting late stage disease.2 Novel strategies to improve early detection respective precursor lesions, dysplasia, Barrett’s esophagus offer potential outcomes. The introduction a limited number biologic agents, as well immune checkpoint inhibitors, resulting in improvements systemic treatment locally advanced metastatic cancer. developments, coupled minimally invasive surgical endoscopic approaches, adaptive precision radiotherapy technologies, outcomes still further. This review summarizes latest advances diagnosis management cancer, developments understanding biology this disease.

Language: Английский

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Recent developments in immunotherapy for gastrointestinal tract cancers

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

Published: Aug. 9, 2024

The past few decades have witnessed the rise of immunotherapy for Gastrointestinal (GI) tract cancers. role immune checkpoint inhibitors (ICIs), particularly programmed death protein 1 (PD-1) and PD ligand-1 antibodies, has become increasingly pivotal in treatment advanced perioperative GI Currently, anti-PD-1 plus chemotherapy is considered as first-line regimen unselected gastric/gastroesophageal junction adenocarcinoma (G/GEJC), mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer (CRC), esophageal (EC). In addition, encouraging performance claudin18.2-redirected chimeric antigen receptor T-cell (CAR-T) therapy later-line cancers brings new hope cell solid tumour treatment. Nevertheless, remains yet precise, researchers are dedicated to further maximising optimising efficacy. This review summarises important research, latest progress, future directions including EC, G/GEJC, CRC.

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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Perioperative outcomes of neoadjuvant chemotherapy plus camrelizumab compared with chemotherapy alone and chemoradiotherapy for locally advanced esophageal squamous cell cancer

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 7, 2023

Purpose Neoadjuvant chemoimmunotherapy (nCIT) is becoming a new therapeutic frontier for resectable esophageal squamous cell carcinoma (ESCC); however, crucial details and technical know-how regarding surgical techniques the perioperative challenges following nCIT remain poorly understood. The study investigated compared advantages disadvantages of esophagectomy with neoadjuvant chemotherapy (nCT) chemoradiotherapy (nCRT). Methods We retrospectively analyzed data patients initially diagnosed ESCC at clinical stage T2-4N+ received therapy followed by Hunan Cancer Hospital between October 2014 February 2021. Patients were divided into three groups according to treatment: (i) nCIT; (ii) nCT; (iii) nCRT. Results There 34 in group, 97 nCT 31 nCRT group. Compared nCT, achieved higher pathological complete response (pCR; 29.0% versus 4.1%, p<0.001) major (MPR; 52.9% 16.5%, rates, more resected lymph nodes during surgery (25.06 ± 7.62 20.64 9.68, p =0.009), less intraoperative blood loss (200.00 73.86 266.49 176.29 mL, =0.035), comparable results other parameters. nCRT, similar pCR (29.0% 25.8%) MPR (52.9% 51.6%, p=0.862) significantly 16.94 7.24, p<0.001), shorter operation time (267.79 50.67 306.32 79.92 min, =0.022), 264.53 139.76 fewer ICU admissions after (29.4% 80.6%, p<0.001). Regarding adverse events complications, no significant statistical differences detected or groups. 3-year overall survival rate was 73.3%, slightly than 46.1% 39.7% statistically (p=0.883). Conclusions This analysis showed that safe feasible, satisfactory rates. Esophagectomy has several over morbidity mortality. long-term benefits still requires further investigation.

Language: Английский

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Induction sintilimab and chemotherapy followed by concurrent chemoradiotherapy for locally advanced esophageal cancer: a proof-of-concept, single-arm, multicenter, phase 2 trial

EClinicalMedicine, Journal Year: 2024, Volume and Issue: 69, P. 102471 - 102471

Published: Feb. 6, 2024

BackgroundConcurrent chemoradiotherapy is the standard nonoperative treatment for locally advanced esophageal squamous cell carcinoma. However, local recurrence still main failure pattern, accounting more than half of all failures, indicating that sensitivity radiotherapy needs to be improved. This trial aimed at demonstrating whether PD-1 inhibitors followed by could promote tumor vascular normalization, alleviate hypoxia, and thus enhance radiosensitivity improve control.MethodsWe did a multicenter, single-arm, phase 2 in China. Patients with cancer were enrolled this study. In induction phase, patients received two cycles sintilimab, paclitaxel carboplatin once per 21 days. concurrent treated five week 50.4Gy delivered 28 fractions. The primary endpoint was 2-year control rate. Hypoxia vessel normalization assessed before after using immunofluorescence perfusion CT. registered ClinicalTrials.gov (NCT03985046).FindingsSeventy-five study between October 2019 April 2021. median follow-up surviving 33.6 months (IQR 29.3–35.7). rate 81.7% (95% confidence interval, 72.7%–90.7%), which much higher chemoradiation only (71.3%) previous studies. Vascular hypoxia alleviation observed both biopsy specimens CT.InterpretationThe addition immunotherapy as non-surgical treatment. New combination led through promoting alleviating hypoxia. Our findings suggest potential option future treatment.FundingNational Natural Science Foundation China Shanghai Rising-Star Program.

Language: Английский

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Immunotherapy for esophageal cancer: Where are we now and where can we go

World Journal of Gastroenterology, Journal Year: 2024, Volume and Issue: 30(19), P. 2496 - 2501

Published: May 17, 2024

Immune checkpoint inhibitor therapy has dramatically improved patient prognosis, and thereby transformed the treatment in various cancer types including esophageal squamous cell carcinoma (ESCC) past decade. Monoclonal antibodies that selectively inhibit programmed death-1 (PD-1) activity now become standard of care ESCC metastatic settings, a high expectation to provide clinical benefit during perioperative period. Further, anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) monoclonal antibody also been approved recurrent/metastatic combination with anti-PD-1 antibody. Well understanding existing evidence immune-based treatments for ESCC, as well recent trials on combinations chemotherapy different settings neoadjuvant, adjuvant, diseases, may future prospects better outcomes.

Language: Английский

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Advancing Esophageal Cancer Treatment: Immunotherapy in Neoadjuvant and Adjuvant Settings

Cancers, Journal Year: 2024, Volume and Issue: 16(2), P. 318 - 318

Published: Jan. 11, 2024

Locally advanced esophageal cancer (LAEC) poses a significant and persistent challenge in terms of effective treatment. Traditionally, the primary strategy for managing LAEC has involved concurrent neoadjuvant chemoradiation followed by surgery. However, achieving pathologic complete response (pCR) proven to be inconsistent, despite treatment, roughly half patients experience locoregional recurrence or metastasis. Consequently, there been paradigm shift towards exploring potential immunotherapy reshaping landscape management. Recent research particularly focused on immune checkpoint inhibitors, investigating their application both adjuvant settings. These designed block specific proteins cells, are meant enhance system's ability target combat cells. Emerging evidence from these studies suggests possibility mortality benefit, indicating that may contribute improved overall survival rates individuals grappling with cancer. This manuscript aims meticulously review existing literature surrounding context The intention is thoroughly examine methodologies findings relevant studies, providing comprehensive synthesis current understanding impact

Language: Английский

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Single-cell profiling of response to neoadjuvant chemo-immunotherapy in surgically resectable esophageal squamous cell carcinoma

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

Published: April 2, 2024

Abstract Background The efficacy of neoadjuvant chemo-immunotherapy (NAT) in esophageal squamous cell carcinoma (ESCC) is challenged by the intricate interplay within tumor microenvironment (TME). Unveiling immune landscape ESCC context NAT could shed light on heterogeneity and optimize therapeutic strategies for patients. Methods We analyzed single cells from 22 baseline 24 post-NAT treatment samples stage II/III patients to explore association between pathological response anti-PD-1 combination therapy, including complete (pCR), major (MPR), incomplete (IPR). Results Single-cell profiling identified 14 subsets cancer, immune, stromal cells. Trajectory analysis unveiled an interesting link cancer differentiation NAT. tumors enriched with less differentiated exhibited a potentially favorable NAT, while clusters more may resist treatment. Deconvolution transcriptomes pre-treatment gene signatures contributed specific populations. Upregulated genes associated better responses CD8 + effector T primarily involved interferon-gamma (IFNγ) signaling, neutrophil degranulation, negative regulation apoptotic process, whereas downregulated were dominated those response-activating surface receptor signaling pathway. Natural killer pCR showed similar upregulation expression IFNγ but downregulation neutrophil-mediated immunity pathways. A decreased cellular contexture regulatory TME indicated Cell–cell communication revealed extensive interactions CCL5 its CCR5 various tumors. Immune checkpoint interaction pairs, CTLA4-CD86, TIGIT-PVR, LGALS9-HAVCR2, TNFSF4-TNFRSF4, might serve as additional targets ICI therapy ESCC. Conclusions This pioneering study intriguing patients, revealing distinct subgroups which be effective. also delineated clinical provides insights understanding how respond further identifying novel future.

Language: Английский

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