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Different immune contextures underlie tumor site-specific responses to immune checkpoint blockade in esophageal cancer.

ABSTRACT: Immune checkpoint inhibitors (ICIs) have demonstrated efficacy in advanced esophageal squamous cell carcinoma (ESCC). Heterogeneous responses to ICIs have been reported previously. Here, we describe a patient with advanced ESCC exhibiting a response to durvalumab plus tremelimumab for more than 6 months except primary resistant esophageal tumor. The esophageal tumor had higher regulatory T cells, neutrophils, and mast cells scores estimated by NanoString platform than hepatic tumor. The immunohistochemistry study confirmed higher expression levels of Foxp3, and myeloperoxidase (MPO) in the esophageal tumor. The different immune contextures may underlie the heterogeneous responses to ICI combination in this ESCC patient.

SUBMITTER: Guo JC

PROVIDER: S-EPMC10396778 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Different immune contextures underlie tumor site-specific responses to immune checkpoint blockade in esophageal cancer.

Guo Jhe-Cyuan JC Hsu Chia-Lang CL Hsieh Min-Shu MS Lin Chia-Chi CC Huang Ta-Chen TC Kuo Hung-Yang HY Shao Yu-Yun YY Hsu Chih-Hung CH

Thoracic cancer 20230620 22

Immune checkpoint inhibitors (ICIs) have demonstrated efficacy in advanced esophageal squamous cell carcinoma (ESCC). Heterogeneous responses to ICIs have been reported previously. Here, we describe a patient with advanced ESCC exhibiting a response to durvalumab plus tremelimumab for more than 6 months except primary resistant esophageal tumor. The esophageal tumor had higher regulatory T cells, neutrophils, and mast cells scores estimated by NanoString platform than hepatic tumor. The immunohi ...[more]

PMID: 37340770

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Project description:Despite the initial successes of immunotherapy, there is an urgent clinical need for molecular assays that identify patients more likely to respond. Here, we report that ultrasensitive measures of circulating tumor DNA (ctDNA) and T-cell expansion can be used to assess responses to immune checkpoint blockade in metastatic lung cancer patients (N = 24). Patients with clinical response to therapy had a complete reduction in ctDNA levels after initiation of therapy, whereas nonresponders had no significant changes or an increase in ctDNA levels. Patients with initial response followed by acquired resistance to therapy had an initial drop followed by recrudescence in ctDNA levels. Patients without a molecular response had shorter progression-free and overall survival compared with molecular responders [5.2 vs. 14.5 and 8.4 vs. 18.7 months; HR 5.36; 95% confidence interval (CI), 1.57-18.35; P = 0.007 and HR 6.91; 95% CI, 1.37-34.97; P = 0.02, respectively], which was detected on average 8.7 weeks earlier and was more predictive of clinical benefit than CT imaging. Expansion of T cells, measured through increases of T-cell receptor productive frequencies, mirrored ctDNA reduction in response to therapy. We validated this approach in an independent cohort of patients with early-stage non-small cell lung cancer (N = 14), where the therapeutic effect was measured by pathologic assessment of residual tumor after anti-PD1 therapy. Consistent with our initial findings, early ctDNA dynamics predicted pathologic response to immune checkpoint blockade. These analyses provide an approach for rapid determination of therapeutic outcomes for patients treated with immune checkpoint inhibitors and have important implications for the development of personalized immune targeted strategies.Significance: Rapid and sensitive detection of circulating tumor DNA dynamic changes and T-cell expansion can be used to guide immune targeted therapy for patients with lung cancer.See related commentary by Zou and Meyerson, p. 1038.

Dataset Information

Different immune contextures underlie tumor site-specific responses to immune checkpoint blockade in esophageal cancer.

Publications

Different immune contextures underlie tumor site-specific responses to immune checkpoint blockade in esophageal cancer.

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