Development of an Automatic Measurement Method for CD8 and PD-1 Positive T Cells Using Image Analysis Software

Anticancer Res. 2022 Jan;42(1):419-427. doi: 10.21873/anticanres.15500.

Abstract

Background/aim: With the progress in cancer immunotherapy using immune checkpoint blockade (ICB) therapy, histological observations of tumor-infiltrating lymphocyte (TIL) status are needed to evaluate the antitumor effect of ICB using imaging analysis software.

Materials and methods: Formalin-fixed paraffin-embedded sections obtained from colorectal cancer and gastric cancer patients with more than 500 single nucleotide variants were stained with anti-CD8 and anti-PD-1 antibodies. Based on our own algorithm and imaging analysis software, an automatic TIL measurement method was established and compared to the manual counting methods.

Results: In the CD8+ T cell number measurement, there was a good correlation (r=0.738 by Pearson test) between the manual and automated counting methods. However, in the PD-1+ T cell measurement, there was a large difference in TIL numbers in both groups. After adjustment of the parameter settings, the correlation between the manual and automated methods in the PD-1+ T cell measurements improved (r=0.668 by Pearson test).

Conclusion: An imaging software-based automatic measurement could be a simple and useful tool for evaluating the therapeutic effect of cancer immunotherapies in terms of TIL status.

Keywords: Tumor microenvironment (TME); automatic measurement; digital pathology; imaging analysis software; project HOPE; tumor-infiltrating lymphocytes (TILs).

MeSH terms

  • Antibodies, Anti-Idiotypic / immunology
  • Antibodies, Anti-Idiotypic / pharmacology
  • CD8 Antigens / genetics*
  • CD8 Antigens / isolation & purification
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / pathology
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / therapy
  • Humans
  • Image Processing, Computer-Assisted
  • Immune Checkpoint Inhibitors / therapeutic use
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Male
  • Polymorphism, Single Nucleotide / genetics
  • Programmed Cell Death 1 Receptor / genetics*
  • Programmed Cell Death 1 Receptor / isolation & purification
  • Software
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / immunology
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / therapy

Substances

  • Antibodies, Anti-Idiotypic
  • CD8 Antigens
  • Immune Checkpoint Inhibitors
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor