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840 Presence and distribution of immunosuppressive peptide P3028 in relation to immune phenotype of tonsillar cancer
  1. Sabine Swoboda1,
  2. Rebecca Rosberg2,
  3. David Gomez Jimenez3,
  4. David Askmyr1,
  5. Malin Lindstedt3,
  6. Lennart Greiff1 and
  7. Leif Håkansson4
  1. 1Skåne University Hospital, Lund, Sweden
  2. 2Canimguide Therapeutics AB, Lund, Sweden
  3. 3Lund University, Lund, Sweden
  4. 4Canimguide Therapeutic AB, Lund, Sweden

Abstract

Background A cancer lesion may avoid detection by the immune system through a variety of immunosupressive mechanisms involving myeloid-derived suppressor cells and regulatory T-cells. One such mechanism recently discovered is the immuno¬suppressive effect of a specific peptide, i.e., P3028, produced through degradation of albumin. In this study, involving biopsies obtained from patients with tonsillar cancer (TC), P3028 is assessed in relation to overall immune phenotype, as indicated by presence and distribution of CD8+ T-cells as well as to other specific immune cells.

Methods Immunohistochemistry was performed on fresh frozen biopsies. CD8+ T-cells were used to classify the cancer lesions into immune phenotypes: ‘inflamed’ (lympho¬cytes infiltrating cancer cell areas), ‘immune excluded’ (lymphocytes in surrounding stroma, but few within cancer cell areas) and ‘desert’ (few lymphocytes in cancer cell areas and in surrounding stroma). P3028 was graded (semi-quantitatively) as high or low. Quantitative flow cytometry was performed focusing on CD8+, CD3+, and CD4+ T-cells, macrophages and dendritic cells.

The study was approved by the Swedish Ethical Review Authority (no. 2017/580). Written informed consent was obtained from the patients. A copy of the written consent is available for review by the Editor of this journal.

Results Based on immunohistochemistry focusing on presence and distribution of CD8+ T-cells, most TC lesions were found to be of an ‘inflamed’ immune phenotype. This particular phenotype also featured low expression of immunosuppressive peptide P3028 (cf. other immune phenotypes). Flow cytometry verified that ‘immune excluded’ and ‘inflamed’ cancer lesions were associated with high levels of CD8+ T-cells (cf. desert lesions). The presence of CD3+ and CD4+ T-cells as well as macrophages and dendritic cells in relation to immune phenotypes were indicated.

Conclusions TC lesions may be classified into ‘inflamed’, ‘immune excluded’, and ‘desert’ phenotypes based on presence and distribution of CD8+ T-cells. Other immune cells may be associated with these immune phenotypes, including CD3+ and CD4+ T-cells, macro¬phages, and dendritic cells. P3028 is present in TC lesions: low levels of this immunosuppressive peptide are observed in the ‘inflamed’ phenotype. Arguably, P3028 prevents successful recruitment of immune cells in TC. Inferentially, presence and distribution of P3028 may be considered as a prognostic marker as well as a treatment target of this condition.

Ethics Approval The study was approved by the Swedish Ethical Review Authority (no. 2017/580).

Consent Written informed consent was obtained from the patients. A copy of the written consent is available for review by the Editor of this journal.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

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