Prognostic assessment of T-cells in primary colorectal cancer and paired synchronous or metachronous liver metastasis

Abstract

Prognostic value of T-cells between primary colorectal cancer (pCRC) and its paired synchronous and metachronous liver metastasis (LM) is underinvestigated and is the subject of the present study. We enrolled into this retrospective cohort study patients, who underwent resection of both pCRC and synchronous LM (N = 55) or metachronous LM (N = 44). After immunohistochemical staining for CD3+, CD8+, and CD45R0+ whole slides were scanned and T-cell densities were quantified using QuPath software in tumor center (TC), inner margin (IM), outer margin (OM), and peritumor zone (PT) of pCRC and LM. High densities of CD8+ T-cells in TC, OM and PT of synchronous LM were associated with longer disease-free survival (DFS). Greater densities of CD3+ T-cells in IM and PT and CD8+ T-cells in IM, OM and PT in synchronous LM over pCRC were associated with longer DFS. Greater densities of CD8+ T-cells in the TC and IM and CD3+ T-cells in the IM of pCRC were found in the metachronous over synchronous group. The first novel finding demonstrated that high density of CD8+ T cells in synchronous LM were associated with favorable outcome. The second finding of high CD8+ cell density in pCRC in metachronous over synchronous CRC may provide a mechanistic basis for the delay of metastatic spread. Both findings could be applied clinically with own reference values.

Keywords: colorectal cancer; survival; synchronous and metachronous liver metastases; tumor‐infiltrating lymphocytes.

FIGURE 1

Statistics depicting the spatial distribution of CD3+, CD8+, and CD45RO+ tumor infiltrating lymphocytes per mm² of the section in the TC, IM, OM, and PT of pCRC and LM in patients with synchronous (left panel, filled symbols) and metachronous disease (right panel, empty symbols). Black lines: medians. *p < 0.05, **p < 0.01, ****p < 0.0001. IM, inner invasive margin; LM, liver metastases; OM, outer invasive margin; pCRC, primary tumor; PT, peritumor zone; TC, tumor center.

FIGURE 2

Kaplan–Meier analysis for DFS according to high versus low densities of T cells per ROI. p values according to log‐rank test. LM, liver metastases; OM, outer invasive margin; PT, peritumor zone; TC, tumor center.

FIGURE 3

Kaplan–Meier analysis for DFS according to greater T cell densities in specific ROI of LM (LM > pCRC) versus smaller cell densities in specific ROI of LM compared to pCRC (LM < pCRC). p values according to log‐rank test. IM, inner invasive margin; LM, liver metastases; OM, outer invasive margin; PT, peritumor zone; ROI, region of interest.