Herter, J. M., Kiljan, M., Kunze, S., Reinscheid, M., Ibruli, O., Cai, J., Niu, L., Hesselmann, I, Trommer, M., Herter-Sprie, G. S., Koehler, C. and Marnitz, S. (2023). Influence of chemoradiation on the immune microenvironment of cervical cancer patients. Strahlenther. Onkol., 199 (2). S. 121 - 131. HEIDELBERG: SPRINGER HEIDELBERG. ISSN 1439-099X

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Abstract

Purpose Cervical cancer remains a leading cause of cancer death in women. While immunotherapy has shown great success in combating cancer, the value of immunotherapy in cervical cancer is still only beginning to be explored. Thus, we performed a prospective analysis of patient blood and tumor samples at the beginning and end of conventional chemoradiation to assess changes in the immune cell and immunoreceptor compartments, and investigate if and when the addition of immunotherapy could be beneficial. Methods Patients with FIGO II-III cervical cancer receiving standard chemoradiation between January 2020 and December 2021 were included. We collected tumor and blood samples from patients before and at the end of therapy and analyzed immune cell composition and immune checkpoint receptor expression on both immune and tumor cells using multicolor flow cytometry. Results In all, 34 patients were eligible in the study period; 22 could be included and analyzed in this study. We found that chemoradiation significantly reduces T cell numbers in both tumors and blood, but increases macrophage and neutrophil numbers in tumors. Furthermore, we found that the percentage of immune checkpoint receptor PD-1 and TIGIT-expressing cells in tumors was significantly reduced at the end of therapy and that CD4 and CD8 memory T cell populations were altered by chemoradiation. In addition, we observed that while PD-L1 expression intensity was upregulated by chemoradiation on blood CD8 cells, PD-L1 expression frequency and the expression intensity of antigen-presenting molecule MHC-I were significantly reduced on tumor cells. Conclusion Our data demonstrate that chemoradiation significantly alters the immune cell composition of human cervical tumors and the expression of immune checkpoint receptors on both lymphocytes and tumor cells. As our results reveal that the percentage of PD-1(+) CD8 cells in the tumor as well as the frequency of PD-L1-expressing tumor cells were reduced at the end of therapy, neoadjuvant or simultaneous anti-PD-1 or anti-PD-L1 treatment might provide better treatment efficiency in upcoming clinical studies.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Herter, J. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kiljan, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kunze, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reinscheid, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ibruli, O.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cai, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Niu, L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hesselmann, IUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Trommer, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Herter-Sprie, G. S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koehler, C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marnitz, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-667498
DOI: 10.1007/s00066-022-02007-z
Journal or Publication Title: Strahlenther. Onkol.
Volume: 199
Number: 2
Page Range: S. 121 - 131
Date: 2023
Publisher: SPRINGER HEIDELBERG
Place of Publication: HEIDELBERG
ISSN: 1439-099X
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
BLOOD LYMPHOCYTE SUBPOPULATIONS; HUMAN-PAPILLOMAVIRUS TYPE-16; SQUAMOUS-CELL CARCINOMA; CONCURRENT CISPLATIN; RADIATION-THERAPY; PELVIC IRRADIATION; RANDOMIZED-TRIAL; OPEN-LABEL; RADIOTHERAPY; CHEMOTHERAPYMultiple languages
Oncology; Radiology, Nuclear Medicine & Medical ImagingMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/66749

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