TY  - JOUR
AU  - Rothe, Rebecca
AU  - Tunger, Antje
AU  - Link, Theresa
AU  - Lai, Xixi
AU  - Kuhlmann, Jan Dominik
AU  - Wimberger, Pauline
AU  - Schmitz, Marc
AU  - Wehner, Rebekka
TI  - Multi-compartment immune cell profiling highlights the prognostic relevance of CD127+ CD8+ T cells for patients with high-grade serous ovarian cancer.
JO  - Frontiers in immunology
VL  - 16
SN  - 1664-3224
CY  - Lausanne
PB  - Frontiers Media
M1  - DKFZ-2025-02379
SP  - 1607471
PY  - 2025
AB  - Ovarian cancer (OC) is a heterogeneous tumor entity with accumulated ascitic fluid in the peritoneal cavity, especially in advanced tumors. In general, a high immune cell infiltration has a favorable effect on OC patients' outcomes. However, the composition of immune cells within the individual compartments of OC-associated locations may differ in their impact on patient prognosis. Therefore, we comprehensively investigated immune cell frequencies in matched peripheral blood, ascites, and tumor samples of 24 high-grade serous OC patients by flow cytometry and associated them with clinical parameters. Immune cell analysis demonstrated that the general immune cell infiltration was comparable between the three investigated compartments, with decreased proportions of CD8+ T cells in advanced stage OC. In addition, immune cell subsets varied significantly in their differentiation and phenotypic marker expression. In peripheral blood, classical monocytes, mature natural killer (NK) cells with cytotoxic potential (CD57+, CD16+, NKG2D+), and less differentiated T cells were more frequent. On the contrary, dendritic cells, and NKp46+ NK cells were prevalent in ascites. In OC tissues, high frequencies of immature neutrophils, CD16- NK cells, and effector memory T cells were found, although the intratumoral T cell frequency was significantly reduced compared to the two liquid samples. Additionally, T cell profiling showed high expression of one or multiple activating and inhibitory receptors in tumor samples. In particular, significant positive correlations of CD127+ CD8+ T cells among all three compartments were shown. Our results provide evidence that a higher proportion of peripheral CD127+ CD8+ T cells, which are memory T cells with low granzyme B production, was a prognostic biomarker for unfavorable progression-free survival of high-grade OC patients, independent of FIGO stage III/IV or residual tumor after surgery.
KW  - Humans
KW  - Female
KW  - Ovarian Neoplasms: immunology
KW  - Ovarian Neoplasms: pathology
KW  - Ovarian Neoplasms: mortality
KW  - CD8-Positive T-Lymphocytes: immunology
KW  - CD8-Positive T-Lymphocytes: metabolism
KW  - Prognosis
KW  - Middle Aged
KW  - Interleukin-7 Receptor alpha Subunit: metabolism
KW  - Interleukin-7 Receptor alpha Subunit: immunology
KW  - Aged
KW  - Cystadenocarcinoma, Serous: immunology
KW  - Cystadenocarcinoma, Serous: pathology
KW  - Cystadenocarcinoma, Serous: mortality
KW  - Adult
KW  - Neoplasm Grading
KW  - Killer Cells, Natural: immunology
KW  - Lymphocytes, Tumor-Infiltrating: immunology
KW  - Lymphocytes, Tumor-Infiltrating: metabolism
KW  - gynecologic cancer (Other)
KW  - immunological biomarker (Other)
KW  - immunophenotyping (Other)
KW  - liquid biopsy (Other)
KW  - local and peripheral immune system (Other)
KW  - tumor microenvironment (Other)
KW  - Interleukin-7 Receptor alpha Subunit (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:41221283
C2  - pmc:PMC12597928
DO  - DOI:10.3389/fimmu.2025.1607471
UR  - https://inrepo02.dkfz.de/record/305762
ER  -