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. 2022 Aug;71(8):1937-1947.
doi: 10.1007/s00262-021-03127-8. Epub 2021 Dec 20.

Alterations of circulating lymphocyte subsets in patients with colorectal carcinoma

Johanna Waidhauser  1   2 , Pia Nerlinger  3 , Tim Tobias Arndt  4   5 , Stefan Schiele  4 , Florian Sommer  6 , Sebastian Wolf  6 , Phillip Löhr  3 , Stefan Eser  7 , Gernot Müller  4 , Rainer Claus  3 , Bruno Märkl  5 , Andreas Rank  3
Affiliations

Alterations of circulating lymphocyte subsets in patients with colorectal carcinoma

Johanna Waidhauser et al. Cancer Immunol Immunother. 2022 Aug.

Abstract

Introduction: Cellular immune response to cancer is known to be of great importance for tumor control. Moreover, solid tumors influence circulating lymphocytes, which has been shown for several types of cancer. In our prospective study we elucidate changes in lymphocyte subsets in patients with colorectal carcinoma compared to healthy volunteers.

Methods: Flow cytometry was performed at diagnosis of colon carcinoma to analyze B cells, T cells and NK cells including various subtypes of each group. Univariate and multivariate analyses including age, gender, tumor stage, sidedness and microsatellite instability status (MSI) were performed.

Results: Forty-seven patients and 50 healthy volunteers were included. Median age was 65 years in patients and 43 years in the control group. Univariate analysis revealed lower total lymphocyte counts, lower CD4 + cells, CD8 + cells, B cells and NKs including various of their subsets in patients. In multivariate analysis patients had inferior values of B cells, CD4 + cells and NK cells and various subsets, regardless of age and gender. Naïve, central memory and HLADR + CD8 + cells showed an increase in patients whereas all other altered subsets declined. MSI status had no influence on circulating lymphocytes except for higher effector memory CD8 + cells in MSI-high patients. Localization in the left hemicolon led to higher values of total cytotoxic T cells and various T cell subsets.

Conclusion: We found significant changes in circulating lymphocyte subsets in colon carcinoma patients, independent of physiological alterations due to gender or age. For some lymphocyte subsets significant differences according to tumor localization or MSI-status could be seen.

Keywords: Cellular immune status; Circulating lymphocytes; Colorectal carcinoma; Flow cytometry; Tumor immune response.

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Conflict of interest statement

The authors declare no potential conflicts of interest.

Figures

Fig. 1
Fig. 1
Comparison of lymphocyte subsets between colon carcinoma patients (red) and healthy controls (gray). A Main lymphocyte subsets, B B cell subsets, C T cell subsets, D CD4 + T cell subsets, E CD8 + T cell subsets. White ticks indicate the individual data points; dotted lines show the overall subset average. Significant p values are displayed with * for p < 0.05 and ** for p < 0.005
Fig. 2
Fig. 2
Age-dependent distribution of cell counts and median decrease over lifetime. Black line = smoothed means of log-transformed data, 95% confidence interval in gray. A total lymphocytes, B CD8 + lymphocytes, C naïve CD8 + lymphocytes, D early CD8 + lymphocytes in the entire cohort
Fig. 3
Fig. 3
Impact of age, gender and colon carcinoma on lymphocyte subsets as calculated in multivariate analysis. A Main lymphocyte subsets, B B cell subsets, C T cell subsets, D CD4 + T cell subsets, E CD8 + T cell subsets
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