Abstract
BackgroundTumor-infiltrating lymphocytes (TILs) have important roles in predicting tumor therapeutic responses and progression, however, the method of evaluating TILs is complicated. We attempted to explore the association of TILs with clinicopathological characteristics and blood indicators, and to develop nomograms to predict the density of TILs in patients with high-grade serous ovarian cancer (HGSOC).MethodsThe clinical profiles of 197 consecutive postoperative HGSOC patients were retrospectively analyzed. Tumor tissues and matched normal fallopian tubes were immunostained for CD3+, CD8+, and CD4+ T cells on corresponding tissue microarrays and the numbers of TILs were counted using the NIH ImageJ software. The patients were classified into low- or high-density groups for each marker (CD3, CD4, CD8). The associations of the investigated TILs to clinicopathological characteristics and blood indicators were assessed and the related predictors for densities of TILs were used to develop nomograms; which were then further evaluated using the C-index, receiver operating characteristic (ROC) curves and calibration plots.ResultsMenopausal status, estrogen receptor (ER), Ki-67 index, white blood cell (WBC), platelets (PLT), lactate dehydrogenase (LDH), and carbohydrate antigen 153 (CA153) had significant association with densities of tumor-infiltrating CD3+, CD8+, or CD4+ T cells. The calibration curves of the CD3+ (C-index = 0.748), CD8+ (C-index = 0.683) and CD4+ TILs nomogram (C-index = 0.759) demonstrated excellent agreement between predictions and actual observations. ROC curves of internal validation indicated good discrimination for the CD8+ TILs nomogram [area under the curve (AUC) = 0.659, 95% CI 0.582–0.736] and encouraging performance for the CD3+ (AUC= 0.708, 95% CI 0.636–0.781) and CD4+ TILs nomogram (AUC = 0.730, 95% CI 0.659–0.801).ConclusionMenopausal status, ER, Ki-67 index, WBC, PLT, LDH, and CA153 could reflect the densities of T cells in the tumor microenvironment. Novel nomograms are conducive to monitor the immune status of patients with HGSOC and help doctors to formulate the appropriate treatment strategies.
Highlights
Ovarian cancer is the most lethal gynecological malignancy worldwide [1]; of which high-grade serous ovarian cancer (HGSOC) accounts for 70–80% of all ovarian cancer-related deaths
This study aimed to explore the association of tumor-infiltrating lymphocytes (TILs) (CD3+, CD8+, and CD4+) to the clinicopathological characteristics and blood indicators of HGSOC; based on which nomograms were established to assess the density levels of TILs, with the hope of providing a convenient method to monitor the immune status of HGSOC patients and help to guide therapeutic strategies in clinical practice
We found that the density of TILs had no significant correlations with neutrophils, lymphocytes, monocytes, Neutrophil-to-lymphocyte ratio (NLR), Platelet-to-lymphocyte ratio (PLR), Lymphocyte-to-monocyte ratio (LMR), ALB, and C-reactive protein (CRP) in the tumor microenvironment (Table 3)
Summary
Ovarian cancer is the most lethal gynecological malignancy worldwide [1]; of which high-grade serous ovarian cancer (HGSOC) accounts for 70–80% of all ovarian cancer-related deaths. TILs refer to mononuclear immune cells (such as white blood cells [WBC], T-cells and B-cells) nested in the tumor stroma or intra-epithelium [9]. It has been well-established that TILs play a crucial role in controlling tumor growth, recognition of cancer antigens, therapeutic response, and the inhibition of cancer development in solid tumors [10, 11]. We attempted to explore the association of TILs with clinicopathological characteristics and blood indicators, and to develop nomograms to predict the density of TILs in patients with high-grade serous ovarian cancer (HGSOC)
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call