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Rectal cancer induces a regulatory lymphocytic phenotype in the tumor-draining lymph nodes to promote cancer cell installation

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Abstract

Tumor-draining lymph nodes (TDLNs) are critical organs, where activation of B cells and T cells is orchestrated. Effector or regulatory anti-tumor immune responses are reflected by the composition of the lymphocytic and monocytic cell population of the node. Aside from the migratory cancer cell abilities, immune cell phenotypic changes in the TDLNs may define nodal invasion by cancer. We assessed the qualitative and quantitative differences between lymphocytic phenotypes in regional TDLNs, in 20 node-negative and 20 node-positive patients (involved and uninvolved nodes) with rectal adenocarcinomas. Benign reactive nodes were also analyzed. CD8+ cells, the main source of cytotoxic T cells, were increased in all TDLNs and, even stronger, in the involved nodes. The percentage of CD4+ cells were significantly increased in negative and uninvolved nodes, while the CD4/CD8 ratio was significantly lower in involved TDLNs. CD25+ and FOXP3+ regulatory lymphocytes, however, prevailed in involved nodes, while uninvolved and negative nodes had a low presence of these regulatory cells. CD20+ B cells were also more abundant in involved nodes. PD-1+ lymphocytes were localized in the germinal centers. A significantly lower percentage of PD-1+ lymphocytes were noted in involved nodes. The development of a regulatory lymphocytic phenotype in the TDLNs appears as an important mechanism that allows cancer cell installation into the nodal environment. As negative/uninvolved TDLNs had a less severe immunosuppression, it is postulated that secreted molecules by cancer cells gradually attenuate the anti-tumor defenses of the TDLNs allowing the subsequent intra-nodal growth of cancer.

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All data reported in the study are available in our Departments.

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Funding

The study has been financially supported by the Tumor and Angiogenesis Research Group.

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Authors and Affiliations

  1. Department of Pathology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece

    Alexandra Giatromanolaki, Paschalis Chatzipantelis, Maria Kouroupi & Konstantina Balaska

  2. Department of Radiotherapy / Oncology, University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece

    Ioannis M. Koukourakis & Michael I. Koukourakis

Authors
  1. Alexandra Giatromanolaki
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  2. Ioannis M. Koukourakis
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  3. Paschalis Chatzipantelis
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  4. Maria Kouroupi
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  6. Michael I. Koukourakis
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Contributions

AG: Conception and design, analysis and interpretation of data, writing of the paper

IMK: Conception and design, analysis and interpretation of data, writing of the paper

PC: Immunohistochemistry assessment, writing of the paper

MaK: Acquisition of data, immunohistochemistry assessment, writing of the paper

KB: Performed the immunohistochemistry, writing of the paper

MIK: Conception and design, analysis and interpretation of data, writing of the paper

Corresponding author

Correspondence to Alexandra Giatromanolaki.

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The authors declare that they have no conflict of interest.

Ethics approval

For the conduct of the study, ethical approval was obtained from the Scientific Committee and the Ethics Research Committees of the University Hospital of Alexandroupolis (study approval number ES11-26-11-18). The patient informed consent was waived by the ethics board, as the study is based on archival material, and the anonymity of patients is guaranteed. The study was conducted according to the criteria set by the declaration of Helsinki.

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Giatromanolaki, A., Koukourakis, I.M., Chatzipantelis, P. et al. Rectal cancer induces a regulatory lymphocytic phenotype in the tumor-draining lymph nodes to promote cancer cell installation. Immunol Res 68, 363–372 (2020). https://doi.org/10.1007/s12026-020-09161-5

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  • DOI: https://doi.org/10.1007/s12026-020-09161-5

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