Tumor-infiltrating lymphoid cells in colorectal cancer patients with varying disease stages and microsatellite instability-high/stable tumors

Salman M. Toor, Varun Sasidharan Nair, Khaled Murshed, Mohamed Abu Nada, Eyad Elkord*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

Immune checkpoint inhibition is an effective anti-cancer therapeutic approach but has shown limited efficacy in treating colorectal cancer (CRC) patients. Importantly, immune constituents of the tumor microenvironment (TME) can influence therapy response and cancer progression. We investigated the expression of immune checkpoints (ICs) on lymphoid populations within the CRC TME and compared with cells from normal colon tissues using samples from 50 patients with varying disease stages. We found that the levels of B cells, T cells, and NK cells were similar, IC-expressing CD4+ and CD4+CD8+ double positive T cells were higher, while CD8+ T cells and CD4CD8 double negative T cells were significantly lower in CRC tumors. Notably, patients with mismatch-repair deficiency/microsatellite instability-high tumors had higher levels of IC-expressing CD4+ and CD8+ T cells than patients with proficient MMR and microsatellite stable tumors. Lastly, The Cancer Genome Atlas Colon Adenocarcinoma datasets showed associations between low expression of selective genes and poorer progression-free interval. Our findings highlight differential expression of ICs on lymphoid cells in CRC tumors in the era of cancer immunotherapy, which at present is solely approved for anti-PD-1 therapy in patients with dMMR/MSI-H tumors. Further investigations into their functionality have potentials for deciphering resistance mechanisms to IC inhibition.

Original languageEnglish
Article number64
Pages (from-to)1-14
Number of pages14
JournalVaccines
Volume9
Issue number1
DOIs
Publication statusPublished - Jan 2021
Externally publishedYes

Keywords

  • B cells
  • Colorectal cancer
  • DMMR
  • Immune checkpoints
  • MSI-H
  • MSS
  • NK cells
  • T cells

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