Immune cell concentrations among the primary tumor microenvironment in colorectal cancer patients predicted by clinicopathologic characteristics and blood indexes

Abstract

Background: Immune cells play a key role in cancer progression and treatment. It is unclear whether the clinicopathologic characteristics and blood indexes of colorectal cancer (CRC) patients could predict immune cell concentrations in the tumor microenvironment.

Methods: CRC patients with detailed data and tumor tissue who visited Sun Yat-sen University Cancer Center between April 1, 2004, and September 1, 2017, were enrolled. The densities of CD3+ and CD8+ T cells examined by immunohistochemistry in both the core of the tumor (CT) and the invasive margin (IM) were summed as the Immunoscore. The relationships between the Immunoscore and clinicopathologic characteristics and blood indexes, including tumor biomarkers (carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9)), inflammatory markers (lactate dehydrogenase (LDH), C-reactive protein (CRP), albumin (ALB), neutrophils, lymphocytes, monocytes, platelets, NLR (neutrophil-to-lymphocyte ratio), PLR (platelet-to-lymphocyte ratio) and LMR (lymphocyte-to-monocyte ratio)) and lipid metabolism markers (cholesterol (CHO), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB)), were analyzed using SPSS.

Results: Older patients had lower CD3+ and CD8+ T cell expression in the IM and a lower Immunoscore than did younger patients. CD8+ T cell expression in the IM and the Immunoscore were lower in right-side tumors than in left-sided tumors. High CD8+ T cell expression in the CT was found in the T4 stage group. The higher the CEA level in the blood, the fewer CD8+ T cells were in the CT. Either fewer monocytes or a higher LMR in the blood, the larger number of CD3+ T cells in the CT. The more ApoA1 was in the blood, the more CD3+ T cells were in both the CT and the IM.

Conclusion: Age, T stage, tumor location, CEA, monocytes, LMR and ApoA1 could reflect immune cells infiltrating the tumor microenvironment of CRC.

Keywords: Blood indexes; Colorectal cancer; Immune cells; Immunoscore; Tumor microenvironment.

Fig. 1

Representative immunohistochemical images of CD3+ and CD8+ T cells in the core of the tumor (CT) and in the invasive margin (IM) of colorectal cancer (200×). a, b Representative images of high-density and low-density CD3+ T cells in the center of the colorectal cancer; c, d Representative images of high-density and low-density CD3+ T cells in the invasive margin of the colorectal cancer; e, f Representative images of high-density and low-density CD8+ T cells in the center of the colorectal cancer; g, h Representative images of high-density and low-density CD8+ T cells in the invasive margin of the colorectal cancer

Fig. 2

Correlations between the CEA level, number of monocytes, LMR, ApoA1 and density of immune cells in the tumor microenvironment. a The density of CD8+ T cells in the core of the tumor showed a tendency that correlated with the level of CEA in the blood, with a coefficient of − 0.135 (P = 0.037). b The density of CD3+ T cells in the core of the tumor was significantly related to the LMR, with a coefficient of 0.135 (P = 0.038). c The density of CD3+ T cells in the core of the tumor showed a tendency that correlated with the number of monocytes in the blood, with a coefficient of − 0.127 (P = 0.052). d The densities of CD3+ T cells in the core of the tumor showed a tendency that correlated with ApoA1, with a coefficient of 0.127 (P = 0.051). e The densities of CD3+ T cells in the invasive margin were correlated with ApoA1, with a coefficient of 0.169 (P = 0.010)