Crosstalk between the gut microbiome and clinical response in locally advanced thoracic esophageal squamous cell carcinoma during neoadjuvant camrelizumab and chemotherapy

Xu, Li; Qi, Yinghua; Jiang, Yi; Ji, Yanjun; Zhao, Qiang; Wu, Jie; Lu, Weishan; Wang, Yinjie; Chen, Qixun; Wang, Changchun

doi:10.21037/atm-22-1165

Cited by 13 publications

(15 citation statements)

References 34 publications

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“…26 Given that some patients with low PD-L1 expression experience clinically meaningful benefit, there is a need to explore additional predictive biomarkers, such as tumor mutational burden, immune signatures, and gut microbiota, which may need to be used in tandem with PD-L1 to identify responders. [27][28][29] Clinicians should be aware of the differences between the TPS and CPS as methods of measuring PD-L1 expression. Recent work 30 has suggested that PD-L1 expression fluctuates temporally by site of tumor biopsy or prior chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…microbiota, which may need to be used in tandem with PD-L1 to identify responders. [27][28][29] Clinicians should be aware of the differences between the TPS and CPS as methods of measuring PD-L1 expression. Recent work 30 has suggested that PD-L1 expression fluctuates temporally by site of tumor biopsy or prior chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…The OS benefit observed in Asian studies (RATIONALE-302 and ORIENT-15) for patients with low PD-L1 expression as determined by the CPS, in contrast to the global pembrolizumab-based first- and second-line studies (KEYNOTE-590 and KEYNOTE-181), suggests that factors beyond PD-L1 may also determine the effectiveness of immunotherapy, such as geographic variation or molecular subtypes . Given that some patients with low PD-L1 expression experience clinically meaningful benefit, there is a need to explore additional predictive biomarkers, such as tumor mutational burden, immune signatures, and gut microbiota, which may need to be used in tandem with PD-L1 to identify responders …”

Section: Discussionmentioning

confidence: 99%

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Effectiveness of Immune Checkpoint Inhibitors in Patients With Advanced Esophageal Squamous Cell Carcinoma

et al. 2023

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ImportanceImmune checkpoint inhibitors (ICIs) have improved survival outcomes of patients with advanced esophageal squamous cell carcinoma in both first- and second-line settings. However, the benefit of ICIs in patients with low programmed death ligand 1 (PD-L1) expression remains unclear.ObjectiveTo derive survival data for patient subgroups with low PD-L1 expression from clinical trials comparing ICIs with chemotherapy in esophageal squamous cell carcinoma and to perform a pooled analysis.Data SourcesKaplan-Meier curves from the randomized clinical trials were extracted after a systematic search of Scopus, Embase, PubMed, and Web of Science from inception until October 1, 2021.Study SelectionRandomized clinical trials that investigated the effectiveness of anti–PD-1–based regimens for advanced esophageal squamous cell carcinoma and that reported overall survival (OS), progression-free survival, or duration of response were included in this meta-analysis.Data Extraction and SynthesisKaplan-Meier curves of all-comer populations, subgroups with high PD-L1, and those with low PD-L1 (when available) were extracted from published articles. A graphic reconstructive algorithm was used to calculate time-to-event outcomes from these curves. In studies with unreported curves for subgroups with low PD-L1 expression, KMSubtraction was used to impute survival data. KMSubtraction is a workflow to derive unreported subgroup survival data with from subgroups. An individual patient data pooled analysis including previously reported and newly imputed subgroups was conducted for trials with the same treatment line and PD-L1 scoring system. Data analysis was conducted from January 1, 2022, to June 30, 2022.Main Outcomes and MeasuresPrimary outcomes included Kaplan-Meier curves and hazard ratios (HRs) for OS for subgroups with low PD-L1 expression. Secondary outcomes included progression-free survival and duration of response.ResultsThe randomized clinical trials CheckMate-648, ESCORT-1st, KEYNOTE-590, ORIENT-15, KEYNOTE-181, ESCORT, RATIONALE-302, ATTRACTION-3, and ORIENT-2 were included, totaling 4752 patients. In the pooled analysis of first-line trials that evaluated a tumor proportion score (CheckMate-648 and ESCORT-1st), no significant benefit in OS was observed with immunochemotherapy compared with chemotherapy in the subgroup of patients who had a tumor proportion score lower than 1% (HR, 0.91; 95% CI, 0.74-1.12; P = .38) compared with chemotherapy. In the pooled analysis of first-line trials that evaluated combined positive score (KEYNOTE-590 and ORIENT-15), there was a significant but modest OS benefit for immunochemotherapy compared with chemotherapy in the subgroup with a combined positive score lower than 10 (HR, 0.77; 95% CI, 0.62-0.94; P = .01).Conclusions and RelevanceFindings suggest a lack of survival benefit of ICI-based regimens in the first-line setting compared with chemotherapy alone in the subgroup with a tumor proportion score lower than 1%.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Effectiveness of Immune Checkpoint Inhibitors in Patients With Advanced Esophageal Squamous Cell Carcinoma

et al. 2023

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“…The use of circulating tumor DNA (ctDNA) to assess MRD shows promise in screening suitable populations for postoperative adjuvant therapy and consolidation therapy after definitive chemoradiotherapy ( 102 – 105 ). Various molecular biomarkers have been identified to predict the response to neoadjuvant chemoradiotherapy for esophageal cancer, as well as various lymphocyte subsets and lymphocyte ratios in the peripheral blood/tumor area, dendritic cells, cytokines, and gut microbiota, have also been reported to have predictive value ( 35 , 44 , 106 – 110 ). However, these biomarkers are not yet widely utilized in clinical practice, and further research is required to determine whether they can predict the effectiveness of immunotherapy in combination with radiotherapy.…”

Section: Discussion: Current Progress and Future Directionmentioning

confidence: 99%

Radiotherapy combined with immune checkpoint inhibitors in locally advanced/metastatic esophageal squamous cell carcinoma: clinical trials, efficacy and future directions

Jiang

Liu

et al. 2023

Front. Immunol.

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Esophageal squamous cell carcinoma (ESCC) is a common malignancy worldwide and often diagnosed at advanced stages with poor prognosis. Combination of radiotherapy and immunotherapy seems to be a promising approach for treating ESCC. This comprehensive review article summarizes the current state of combination of radiotherapy and immunotherapy in locally advanced/metastatic ESCC, delineates the clinical trials that merit attention, and outlines unresolved issues and future research directions in this field. The clinical trial findings suggest that radio-immunotherapy combination may improve tumor response and overall survival with manageable side effects, highlighting the importance of patient selection and the necessity for further research to optimize treatment strategies. Issues such as irradiation dosage, fractionation regimen, irradiation site and technique of radiotherapy, as well as the timing, sequence and duration of combination therapy will all affect treatment outcomes, justifying further in-depth investigation.

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“…In recent years, neoadjuvant immunotherapy has emerged as a rapidly developing treatment option for cancer patients [ 79 ]. Xu et al found that taxonomic features of the gut microbiome can predict the pathological response and severe adverse events (≥ 3 grade) in esophageal squamous cell carcinoma (ESCC) patients who were undergoing neoadjuvant camrelizumab and chemotherapy [ 67 ], which further expands the potential applications for gut microbiome biomarkers.…”

Section: Prediction Of Iraes By Gut Microbiomementioning

confidence: 99%

Role of gut microbiome in cancer immunotherapy: from predictive biomarker to therapeutic target

Zhang,

Liu,

Xia

2023

Exp Hematol Oncol

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Immunotherapy has emerged as an effective treatment for various types of cancers. Recent studies have highlighted a significant correlation between the gut microbiome and patients’ response to immunotherapy. Several characteristics of the gut microbiome, such as community structures, taxonomic compositions, and molecular functions, have been identified as crucial biomarkers for predicting immunotherapy response and immune-related adverse events (irAEs). Unlike other -omics, the gut microbiome can serve as not only biomarkers but also potential targets for enhancing the efficacy of immunotherapy. Approaches for modulating the gut microbiome include probiotics/prebiotics supplementation, dietary interventions, fecal microbiota transplantation (FMT), and antibiotic administration. This review primarily focuses on elucidating the potential role of the gut microbiome in predicting the response to cancer immunotherapy and improving its efficacy. Notably, we explore reasons behind inconsistent findings observed in different studies, and highlight the underlying benefits of antibiotics in liver cancer immunotherapy.

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Crosstalk between the gut microbiome and clinical response in locally advanced thoracic esophageal squamous cell carcinoma during neoadjuvant camrelizumab and chemotherapy

Cited by 13 publications

References 34 publications

Effectiveness of Immune Checkpoint Inhibitors in Patients With Advanced Esophageal Squamous Cell Carcinoma

Effectiveness of Immune Checkpoint Inhibitors in Patients With Advanced Esophageal Squamous Cell Carcinoma

Radiotherapy combined with immune checkpoint inhibitors in locally advanced/metastatic esophageal squamous cell carcinoma: clinical trials, efficacy and future directions

Role of gut microbiome in cancer immunotherapy: from predictive biomarker to therapeutic target

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