Dataset Information

Rapid Serial Immunoprofiling of the Tumor Immune Microenvironment by Fine Needle Sampling.

ABSTRACT:

Purpose

There is increasing effort to discover and integrate predictive and/or prognostic biomarkers into treatment algorithms. While tissue-based methods can reveal tumor-immune cell compositions at a single time point, we propose that single-cell sampling via fine needle aspiration (FNA) can facilitate serial assessment of the tumor immune microenvironment (TME) with a favorable risk-benefit profile.

Experimental design

Primary antibodies directed against 20 murine and 25 human markers of interest were chemically modified via a custom linker-bio-orthogonal quencher (FAST) probe. A FAST-FNA cyclic imaging and analysis pipeline were developed to derive quantitative response scores. Single cells were harvested via FNA and characterized phenotypically and functionally both in preclinical and human samples using the newly developed FAST-FNA assay.

Results

FAST-FNA samples analyzed manually versus the newly developed deep learning-assisted pipeline gave highly concordant results. Subsequently, an agreement analysis showed that FAST and flow cytometry of surgically resected tumors were positively correlated with an R² = 0.97 in preclinical samples and an R² = 0.86 in human samples with the detection of the relevant tumor and immune biomarkers of interest. Finally, the feasibility of applying this minimally invasive approach to analyze the TME during immunotherapy was assessed in patients with cancer revealing local antitumor immune programs.

Conclusions

The FAST-FNA is an innovative technology that combines bio-orthogonal chemistry coupled with a computational analysis pipeline for the comprehensive profiling of single cells obtained through FNA. This is the first demonstration that the complex and rapidly evolving TME during treatment can be accurately and serially measured by simple FNA.

SUBMITTER: Oh J

PROVIDER: S-EPMC8416923 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Publications

Rapid Serial Immunoprofiling of the Tumor Immune Microenvironment by Fine Needle Sampling.

Oh Juhyun J Carlson Jonathan C T JCT Landeros Christian C Lee Hakho H Ferguson Scott S Faquin William C WC Clark John R JR Pittet Mikael J MJ Pai Sara I SI Weissleder Ralph R

Clinical cancer research : an official journal of the American Association for Cancer Research 20210707 17

<h4>Purpose</h4>There is increasing effort to discover and integrate predictive and/or prognostic biomarkers into treatment algorithms. While tissue-based methods can reveal tumor-immune cell compositions at a single time point, we propose that single-cell sampling via fine needle aspiration (FNA) can facilitate serial assessment of the tumor immune microenvironment (TME) with a favorable risk-benefit profile.<h4>Experimental design</h4>Primary antibodies directed against 20 murine and 25 human ...[more]

PMID: 34233961

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Project description:Background and study aims Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) is traditionally considered a first-line strategy for diagnosing pancreatic lesions; however, given less than ideal accuracy rates, fine-needle biopsy (FNB) has been recently developed to yield histological tissue. The aim of this study was to compare diagnostic yield and safety between EUS-FNA and EUS-FNB in sampling of pancreatic masses. Patients and methods This was a multicenter retrospective study to evaluate efficacy and safety of EUS-FNA and EUS-FNB for pancreatic lesions. Baseline characteristics including sensitivity, specificity, and accuracy, were evaluated. Rapid on-site evaluation (ROSE) diagnostic adequacy, cell-block accuracy, and adverse events were analyzed. Subgroup analyses comparing FNA versus FNB route of tissue acquisition and comparison between methods with or without ROSE were performed. Multivariable logistic regression was also performed. Results A total of 574 patients (n = 194 FNA, n = 380 FNB) were included. Overall sensitivity, specificity, and accuracy of FNB versus FNA were similar [(89.09 % versus 85.62 %; P = 0.229), (98.04 % versus 96.88 %; P = 0.387), and 90.29 % versus 87.50 %; P = 0.307)]. Number of passes for ROSE adequacy and cell-block accuracy were comparable for FNA versus FNB [(3.06 ± 1.62 versus 3.04 ± 1.88; P = 0.11) and (3.08 ± 1.63 versus 3.35 ± 2.02; P = 0.137)]. FNA + ROSE was superior to FNA alone regarding sensitivity and accuracy [91.96 % versus 70.83 %; P < 0.001) and (91.80 % versus 80.28 %; P = 0.020)]. Sensitivity of FNB + ROSE and FNB alone were superior to FNA alone [(92.17 % versus 70.83 %; P < 0.001) and (87.44 % versus 70.83 %; P < 0.001)]. There was no difference in sensitivity though improved accuracy between FNA + ROSE versus FNB alone [(91.96 % versus 87.44 %; P = 0.193) and (91.80 % versus 80.72 %; P = 0.006)]. FNB + ROSE was more accurate than FNA + ROSE (93.13 % versus 91.80 % ; P = 0.001). Multivariate analysis showed ROSE was a significant predictor of accuracy [OR 2.60 (95 % CI, 1.41-4.79)]. One adverse event occurred after FNB resulting in patient death. Conclusion EUS-FNB allowed for more consistent cell-block evaluation as compared to EUS-FNA. EUS-FNA + ROSE was found to have a similar sensitivity to EUS-FNB alone suggesting a reduced need for ROSE as part of the standard algorithm of pancreatic sampling. While FNB alone produced similar diagnostic findings to EUS-FNA + ROSE, FNB + ROSE still was noted to increase diagnostic yield. This finding may favor a unique role for FNB + ROSE, suggesting it may be useful in cases when previous EUS-guided sampling may have been indeterminate.

Dataset Information

Rapid Serial Immunoprofiling of the Tumor Immune Microenvironment by Fine Needle Sampling.

Purpose

Experimental design

Results

Conclusions

Publications

Rapid Serial Immunoprofiling of the Tumor Immune Microenvironment by Fine Needle Sampling.

Similar Datasets

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