Clinical Significance of Tumor-Infiltrating Lymphocytes in Malignant Peritoneal Mesothelioma: A Single-Center Study of 143 Cases

Ann Surg Oncol. 2025 Jul;32(7):5051-5062. doi: 10.1245/s10434-025-17437-z. Epub 2025 May 15.

Abstract

Background: Malignant peritoneal mesothelioma (MPM) is a rare malignant tumor with high mortality rate and extremely poor prognosis. The tumor immune microenvironment, particularly tumor-infiltrating lymphocytes (TILs), plays a critical role in disease progression and treatment response. This study aimed to analyze the correlation between the level of TILs and the main clinicopathological characteristics and prognosis of MPM.

Patients and methods: A total of 143 postoperative specimens from patients with MPM following cytoreductive surgery were collected. Postoperative specimens were stained with hematoxylin and eosin (H&E). The level of TILs was quantitatively analyzed by QuPath 0.3.2 software. Univariate and multivariate analyses were conducted to investigate the correlation between TILs level and other conventional clinicopathological characteristics.

Results: Among the 143 patients with MPM, 73 were male (51.0%) and 70 were female (49.0%), with a median age of 55 (range 24-73) years. There were 72 (50.3%) cases with low TILs, and 71 (49.7%) cases with high TILs. Univariate analysis showed that TIL level (low versus high) was negatively correlated with the following seven clinicopathological factors: surgery history, Ki-67 index, preoperative CA125 level, peritoneal cancer index (PCI) index, bleeding volume, red blood cell (RBC) transfusion volume, and ascites volume (all P < 0.05). Multivariate analysis indicated that TIL level was independently negatively correlated with preoperative carbohydrate antigen (CA)125 level (odds ratio 0.394, 95% CI 0.179-0.866, P = 0.020). Cox regression analysis suggested that high TILs was independently associated with better prognosis of MPM. Moreover, a cohort of patients who received preoperative chemotherapy combined with targeted therapy were evaluated for response. Kaplan-Meier curve showed that high infiltration of TILs predicted better overall survival in patients undergoing treatment.

Conclusions: TILs could be a useful indicator for predicting prognosis and guiding personalized treatment strategies in patients with MPM.

Keywords: Clinical significance; Malignant peritoneal mesothelioma; Microenvironment; Tumor infiltrating lymphocytes.

MeSH terms

  • Adult
  • Aged
  • Clinical Relevance
  • Cytoreduction Surgical Procedures
  • Female
  • Follow-Up Studies
  • Humans
  • Lung Neoplasms* / immunology
  • Lung Neoplasms* / pathology
  • Lung Neoplasms* / surgery
  • Lymphocytes, Tumor-Infiltrating* / immunology
  • Lymphocytes, Tumor-Infiltrating* / pathology
  • Male
  • Mesothelioma* / immunology
  • Mesothelioma* / pathology
  • Mesothelioma* / surgery
  • Mesothelioma, Malignant
  • Middle Aged
  • Peritoneal Neoplasms* / immunology
  • Peritoneal Neoplasms* / pathology
  • Peritoneal Neoplasms* / surgery
  • Prognosis
  • Retrospective Studies
  • Survival Rate
  • Tumor Microenvironment
  • Young Adult