Prognostic significance of T cells, PD-L1 immune checkpoint and tumour associated macrophages in clear cell carcinoma of the ovary

Gynecol Oncol. 2021 Aug;162(2):421-430. doi: 10.1016/j.ygyno.2021.05.010. Epub 2021 Jun 2.


Objective: To define the pre-treatment tumour immune landscape of clear cell carcinoma of the ovary (CCOC).

Methods: We investigated the infiltration profiles of selected immune cell populations and immune checkpoint proteins that have been previously shown to have prognostic relevance in high grade serous carcinoma of the ovary to determine their association with clinical outcomes in CCOC patients. Using multiplex immunohistochemistry, we evaluated the density of CD3+, FoxP3+, CD8+ T cells, CD20+ B cells and expression of PD-1, PD-L1 and IDO1 immune checkpoints in a cohort of 162 CCOC tumour specimens on a tissue microarray.

Results: Increased infiltration of CD3+ CD8- (helper T) cells, CD8+ (cytotoxic T) cells, and CD68+ macrophages significantly associated with shorter disease-free survival, recurrence-free survival and overall survival. Importantly, higher expression of PD-L1 and IDO-1 immune checkpoints was associated with better clinical outcomes.

Conclusion: Findings from our study are foundational towards the development of immune classifiers and biomarkers of response to immune checkpoint blockade therapy in CCOC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • B7-H1 Antigen / analysis
  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / metabolism
  • Carcinoma / drug therapy
  • Carcinoma / immunology
  • Carcinoma / mortality*
  • Disease-Free Survival
  • Female
  • Gene Expression Profiling
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology
  • Immune Checkpoint Inhibitors / therapeutic use
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / analysis
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / antagonists & inhibitors
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
  • Lymphocytes, Tumor-Infiltrating / drug effects
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Middle Aged
  • Neoplasm Recurrence, Local / epidemiology*
  • Neoplasm Recurrence, Local / immunology
  • Neoplasm Recurrence, Local / prevention & control
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / mortality*
  • Ovary / immunology*
  • Ovary / pathology
  • Prognosis
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • Tissue Array Analysis
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / immunology*
  • Tumor-Associated Macrophages / drug effects
  • Tumor-Associated Macrophages / immunology


  • B7-H1 Antigen
  • CD274 protein, human
  • IDO1 protein, human
  • Immune Checkpoint Inhibitors
  • Indoleamine-Pyrrole 2,3,-Dioxygenase