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Stratification of chemotherapy-treated stage III colorectal cancer patients using multiplexed imaging and single-cell analysis of T-cell populations.

Colorectal cancer (CRC) has one of the highest cancer incidences and mortality rates. In stage III, postoperative chemotherapy benefits <20% of patients, while more than 50% will develop distant metastases. Biomarkers for identification of patients at increased risk of disease recurrence following a...

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Published in:Modern Pathology Vol. 35; no. 4; pp. 564 - 577
Main Authors: Stachtea, Xanthi, Loughrey, Maurice B., Salvucci, Manuela, Lindner, Andreas U., Cho, Sanghee, McDonough, Elizabeth, Sood, Anup, Graf, John, Santamaria-Pang, Alberto, Corwin, Alex, Laurent-Puig, Pierre, Dasgupta, Sonali, Shia, Jinru, Owens, Jonathan R., Abate, Samantha, Van Schaeybroeck, Sandra, Lawler, Mark, Prehn, Jochen H. M., Ginty, Fiona, Longley, Daniel B.
Format: pictorial research tables/charts Journal Article
Published: Elsevier B.V. Apr2022
Online Access:View this record in EBSCOhost
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      jtl: Modern Pathology
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      dt: Apr2022
      vid: 35
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      pub: Elsevier B.V.
      place: New York, New York
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        10.1038/s41379-021-00953-0
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        atl: Stratification of chemotherapy-treated stage III colorectal cancer patients using multiplexed imaging and single-cell analysis of T-cell populations.
      aug:
        au:
          Stachtea, Xanthi
          Loughrey, Maurice B.
          Salvucci, Manuela
          Lindner, Andreas U.
          Cho, Sanghee
          McDonough, Elizabeth
          Sood, Anup
          Graf, John
          Santamaria-Pang, Alberto
          Corwin, Alex
          Laurent-Puig, Pierre
          Dasgupta, Sonali
          Shia, Jinru
          Owens, Jonathan R.
          Abate, Samantha
          Van Schaeybroeck, Sandra
          Lawler, Mark
          Prehn, Jochen H. M.
          Ginty, Fiona
          Longley, Daniel B.
        affil: Patrick G. Johnston Centre for Cancer Research, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Northern Ireland, UK
      sug:
        subj:
          Cytological Techniques
          Colorectal Neoplasms Pathology
          Prognosis
          Chemotherapy, Adjuvant
          Cell Physiology
          Proteins
          Neoplasm Recurrence, Local Pathology
          Neoplasm Staging
          Funding Source
          Human
      ab: Colorectal cancer (CRC) has one of the highest cancer incidences and mortality rates. In stage III, postoperative chemotherapy benefits <20% of patients, while more than 50% will develop distant metastases. Biomarkers for identification of patients at increased risk of disease recurrence following adjuvant chemotherapy are currently lacking. In this study, we assessed immune signatures in the tumor and tumor microenvironment (TME) using an in situ multiplexed immunofluorescence imaging and single-cell analysis technology (Cell DIVETM) and evaluated their correlations with patient outcomes. Tissue microarrays (TMAs) with up to three 1 mm diameter cores per patient were prepared from 117 stage III CRC patients treated with adjuvant fluoropyrimidine/oxaliplatin (FOLFOX) chemotherapy. Single sections underwent multiplexed immunofluorescence staining for immune cell markers (CD45, CD3, CD4, CD8, FOXP3, PD1) and tumor/cell segmentation markers (DAPI, pan-cytokeratin, AE1, NaKATPase, and S6). We used annotations and a probabilistic classification algorithm to build statistical models of immune cell types. Images were also qualitatively assessed independently by a Pathologist as 'high', 'moderate' or 'low', for stromal and total immune cell content. Excellent agreement was found between manual assessment and total automated scores (p < 0.0001). Moreover, compared to single markers, a multi-marker classification of regulatory T cells (Tregs: CD3+/CD4+FOXP3+/PD1-) was significantly associated with disease-free survival (DFS) and overall survival (OS) (p = 0.049 and 0.032) of FOLFOX-treated patients. Our results also showed that PD1- Tregs rather than PD1+ Tregs were associated with improved survival. These findings were supported by results from an independent FOLFOX-treated cohort of 191 stage III CRC patients, where higher PD1- Tregs were associated with an increase overall survival (p = 0.015) for CD3+/CD4+/FOXP3+/PD1-. Overall, compared to single markers, multi-marker classification provided more accurate quantitation of immune cell types with stronger correlations with outcomes.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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