Low Concordance Between T-Cell Densities in Matched Primary Tumors and Liver Metastases in Microsatellite Stable Colorectal Cancer

Vegar Johansen Dagenborg; Serena Elizabeth Marshall; Krzysztof Grzyb; Åsmund Avdem Fretland; Marius Lund-Iversen; Gunhild Mari Mælandsmo; Anne Hansen Ree; Bjørn Edwin; Sheraz Yaqub; Kjersti Flatmark

doi:10.3389/fonc.2021.671629

Low Concordance Between T-Cell Densities in Matched Primary Tumors and Liver Metastases in Microsatellite Stable Colorectal Cancer

Front Oncol. 2021 Jun 9:11:671629. doi: 10.3389/fonc.2021.671629. eCollection 2021.

Authors

Vegar Johansen Dagenborg^{1

2

3}, Serena Elizabeth Marshall¹, Krzysztof Grzyb⁴, Åsmund Avdem Fretland^{5

6}, Marius Lund-Iversen⁴, Gunhild Mari Mælandsmo^{1

7}, Anne Hansen Ree^{2

8}, Bjørn Edwin^{2

6}, Sheraz Yaqub^{2

5}, Kjersti Flatmark^{1

2

3}

Affiliations

¹ Department of Tumor Biology, Oslo University Hospital, Oslo, Norway.
² Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
³ Department of Gastroenterological Surgery, Oslo University Hospital, Oslo, Norway.
⁴ Department of Pathology, Oslo University Hospital, Oslo, Norway.
⁵ Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, Norway.
⁶ The Intervention Center, Oslo University Hospital, Oslo, Norway.
⁷ Institute of Medical Biology, The Arctic University of Norway-University of Tromsø, Tromsø, Norway.
⁸ Department of Oncology, Akershus University Hospital, Lørenskog, Norway.

Abstract

Background: The subtype, density and location of tumor infiltrating T-cells are being explored as prognostic and predictive biomarkers in primary colorectal cancer (pCRC) and colorectal liver metastases (CLM). Very limited data exist comparing findings in pCRC and matched CLM.

Patients and methods: Fifty-eight patients with available pCRC and matched CLM (57/58 microsatellite stable) were included in this OSLO-COMET substudy. In immunohistochemically stained sections, total (T_tot), helper (TH), cytotoxic (CTL), and regulatory (Treg) T-cells were manually counted in hotspots from the invasive margin (IM), intratumor (IT), and tumor adjacent regions to determine T-cell densities.

Results: A striking accumulation of T-cells was found in IM of both pCRC and CLM with much lower densities in the IT region, exemplified by T_tot of 2838 versus 340 cells/mm², respectively, in CLM. The correlation at the individual level between T-cell densities in pCRC and corresponding CLM was poor for all regions and T-cell subtypes; for instance, the correlation coefficient (R²) for IM T_tot was 0.07. The IT TH : CTL and Treg : TH ratios were 2.94 and 0.44, respectively, in pCRC, and 1.84 and 0.24, respectively, in CLM.

Conclusion: The observed accumulation of T-cells in the IM regions of pCRC and CLM with low penetration to the IT regions, combined with high TH : CTL and Treg : TH ratios, point to the presence of an immune suppressive microenvironment. T-cell densities of CLM differed markedly from the matched pCRC, indicating that to evaluate T-cell biomarkers in metastasis, the commonly available pCRC cannot serve as a surrogate for the metastatic tumor.

Keywords: T cell densities; colorectal cancer; colorectal liver metastases; cytotoxic T cell; helper T cells; regulatory T cells; tumor immune microenvironment.