Microsatellite unstable colorectal cancers are associated with increased CD1a- and CD83-positive dendritic cell infiltration

Abstract

Microsatellite instability (MSI) is characterized by a highly immunogenic tumor phenotype and abundant lymphocytic infiltrates. The aim of this study was to investigate the association between four immunohistochemically determined classes of dendritic cells (DC) with microsatellite instability status of 258 colorectal cancer (CRC) patients and to explore the possible role of those cells as prognostic factors for survival. We observed a distinct infiltration pattern of DCs both in tumor stroma (TS) and invasive front (IF), with DCs significantly prevailing in the IF (p < 0.0001). MSI cancer biopsies showed significantly higher infiltration of CD1a + and CD83+ DCs in the TS and IF compared to microsatellite stable CRCs. Survival analysis revealed that higher CD1a + and CD83+ DC numbers both in TS and IF correlated with longer survival of the patients after surgical therapy (p < 0.05, Log rank test). Cox multivariate analysis showed that lower infiltration with CD1a + DCs in TS (p = 0.039) and CD83+ DCs in IF (p = 0.022) was an independent prognostic factor for unfavorable outcome for CRC patients. The results of our study suggest that the immunohistochemically determined CD1a + and CD83+ DCs could be used as a feature of microsatellite instability and could be further explored as prognostic markers for patients’ outcome.

Keywords:

• CRC
• microsatellite instability (MSI)
• dendritic cells
• immunohistochemistry
• prognostic factor
• survival

Author contributions

Conceptualization, MG; Funding acquisition, MG, TV; Methodology, MG, TV, EA; Software, TV, DC; Validation, MG, TV.; Formal analysis, MG, TV, EA. Investigation, MG, TV, EA.; Resources, MG, YY, PC, DC.; Writing – Original Draft Preparation, MG, TV; Writing – review & editing, MG, TV, YY; Visualization, MG, TV, EA, DC; Supervision, MG.; Validation, MG, TV; Project administration, MG, TV.

Disclosure statement

The authors declare no conflict of interest.

Informed consent statement

Written informed consents were obtained from all participants before the surgical therapy and enrollment in the study.

Institutional review board statement

This work was approved by the Ethics committee at Medical Faculty, Trakia University, Stara Zagora, Bulgaria (Protocol № 9/15.05.2019 and Protocol 18/15.04.2022).

Data availability statement

The raw data are available from the corresponding authors upon reasonable request.

Additional information

Funding

This work was financially supported by the National Science Fund, Bulgarian, Research grant number KP-06-H23/2 from 17.12.2018; by the Bulgarian Ministry of Education and Science (MES) in the frames of National Program "Young scientists and postdoctoral fellows – 2” based on RMS № 206/07.04.2022.; by the Research project 7/2022, by Medical Faculty, Trakia University, Stara Zagora and by Bulgarian Ministry of Education and Science (MES) in the frames of Bulgarian National Recovery and Resilience Plan, Component "Innovative Bulgaria", the Project № BG-RRP-2.004-0006-C02 “Development of research and innovation at Trakia University in service of health and sustainable well-being”.