Lymphocyte-to-monocyte ratio as a prognostic and potential tumor microenvironment indicator in advanced soft tissue sarcoma treated with first-line doxorubicin therapy

Abstract

Prognostic value of hematologic indices and their association with the tumor microenvironment (TME) remain unclear in advanced soft tissue sarcoma (STS). We aimed to evaluate their prognostic value and correlation with the TME status in advanced STS treated with first-line doxorubicin (DXR) therapy. Clinical data and three hematological indices, including lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio, and neutrophil-to-lymphocyte ratio, were collected from 149 patients with advanced STS. The TME status was pathologically examined by CD3, CD68, and CD20 staining of resected tumor slides. In a multivariate Cox analysis, low LMR and absence of primary tumor resection were independently associated with worse overall survival (OS) (HR 3.93, p = 0.001; HR 1.71, p = 0.03). A prognostic model using these variables predicted OS with greater area under curves than those obtained using Systemic Inflammatory Score and Glasgow Prognostic Score. The LMR significantly correlated with the tumoral CD3/CD68-positive cell ratio in surgical specimens (R = 0.959, p = 0.04). In conclusion, LMR was a prognostic factor in advanced STS treated with first-line DXR therapy. LMR could partially reflect anti-tumor immunity in the TME and have the prognostic value. The potential role of LMR as an indicator of TME status warrants further investigation.

Figure 1

Variation in hematological indices among selected patient subgroups. Box plots showing indices according to age, histology, tumor site, presence of primary tumor resection, PS, and presence of metastasis. Each point on the scatter plot represents an individual patient within a specified subgroup. The overlaid box plot presents the median and interquartile range of the indices for all patients. DDLPS, dedifferentiated liposarcoma; LMR, lymphocyte-to-monocyte ratio; NLR, neutrophil-to-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio; PS, performance status; UPS, undifferentiated polymorphic sarcoma. *p < 0.05; **p < 0.01; ***p < 0.001.

Figure 2

OS stratified by LMR (A) and the LMR prognostic score (B). (C) The prognostic potential of the LMR prognostic score was compared with that of SIS or GPS in ROC analyses for OS at 1 year (left), 2 years (middle), and 3 years (right). AUC, area under curve; CI, confidence interval; DXR, doxorubicin; GPS, Glasgow prognostic score; LMR, lymphocyte-to-monocyte ratio; OS, overall survival; SIS, Systemic Inflammatory Score.

Figure 3

(A) Immunohistochemical analysis of the selected surgical samples. The upper images show a leiomyosarcoma with a high LMR of 7.19. The HE-stained (left), CD3-positive (middle left), CD68-positive (middle right), and CD20-positive (right) cells are shown. The lower images show a dedifferentiated liposarcoma with a low LMR of 0.94. Scale bars: 250 μm. (B) Correlation between LMR and the densities of positive cells. Pearson correlation coefficients are shown. HE, hematoxylin and eosin; LMR, lymphocyte-to-monocyte ratio.