Impact of T Cell Ratios on Survival in Pleural Mesothelioma: Insights from Tumor Microenvironment Analysis

Our plain-English summary of Impact of T Cell Ratios on Survival in Pleural Mesothelioma: Insights from Tumor Microenvironment Analysis, by L.V. Klotz, A. Weigert, F. Eichhorn, et al (Cancers, 2024).

The study

• Authors: L.V. Klotz, A. Weigert, F. Eichhorn, M. Allgäuer, T. Muley, R. Shah, R. Savai, M.E. Eichhorn, H. Winter
• Journal: Cancers
• Published: 2024;16(19)
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Immunotherapy has significantly improved overall survival in patients with pleural mesothelioma, yet this benefit does not extend to those with the epithelioid subtype. Tumor growth is believed to be influenced by the immune response. This study aimed to analyze the tumor microenvironment to gain a better understanding of its influence on tumor growth. Methods: The tumor immune cell infiltration of 188 patients with pleural mesothelioma was characterized by multiplex immunofluorescence staining for CD3+ cells (CD3+), CD4+ cells (CD3+/CD4+), CD8+ cells (CD3+/CD8+), Treg (CD3+/CD4+/CD8-/CD163-/Foxp3+), PD1 cells (PD1+), and T helper cells (CD3+/CD4+/CD8-/CD163-/FoxP3-). The distribution of specific immune cells was correlated with clinical parameters. Results: A total of 188 patients with pleural mesothelioma (135 epithelioid, 9 sarcomatoid, 44 biphasic subtypes) were analyzed. The median age was 64.8 years. Overall survival was significantly longer in the epithelioid subtype than in the non-epithelioid subtype (p = 0.016). The presence of PD-L1 expression had a negative effect on overall survival (p = 0.041). A high ratio of CD4+ cells to regulatory T cells was associated with a significantly longer overall survival of more than 12 months (p = 0.015). The ratio of CD4+ cells to regulatory T cells retained its significant effect on overall survival in the multivariate analysis. Conclusions: Distinct differences in the T cell immune infiltrates in mesothelioma are strongly associated with overall survival. The tumor microenvironment could therefore serve as a source of prognostic biomarkers.

In plain English

This retrospective study from the Thoraxklinik Heidelberg in Germany examined tumor tissue from 188 patients with pleural mesothelioma diagnosed by surgical biopsy between 2001 and 2011. Of these, 135 had the epithelioid, 9 the sarcomatoid and 44 the biphasic subtype. 65.4% had known asbestos exposure; fiber types were not reported. The authors used multiplex immunofluorescence staining to count types of T cells (immune cells) in the tumors and compared these counts with survival. Median overall survival was 15.1 months: 17.3 months for epithelioid, 11.4 for biphasic and 6.4 for sarcomatoid tumors (p = 0.016). Patients whose tumors did not express PD-L1 survived significantly longer (p = 0.041). The ratio of CD4+ cells to regulatory T cells was higher in patients who survived more than 12 months (1.584 vs. 0.520; p = 0.015). This ratio remained significantly associated with survival in a multivariate analysis (p = 0.044). The authors concluded that differences in T cell infiltrates are strongly associated with overall survival and that the tumor microenvironment could be a source of prognostic markers. They noted that the study was retrospective and lacked tumor grading data.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective cohort study of archived tumor tissue, using multiplex immunofluorescence staining of tissue microarrays and survival analysis
• Who was studied: 188 patients with histologically confirmed pleural mesothelioma (175 men, 13 women; median age 64.8 years) diagnosed by surgical biopsy at the Thoraxklinik Heidelberg, Germany, between May 2001 and March 2011. 135 had epithelioid, 9 sarcomatoid and 44 biphasic tumors. All received platinum-based chemotherapy, and none were alive at the end of follow-up.
• Exposure: The study measured T cell types in the tumor tissue (CD3+, CD4+, CD8+, regulatory T cells, PD1 cells, T helper cells) and tumor PD-L1 expression. Asbestos exposure was recorded as yes for 123 patients (65.4%), no for 52 (27.7%) and unknown for 13 (6.9%). Fiber types and doses were not reported.
• Main results:
  • Median overall survival in the whole cohort was 15.1 months. By subtype it was 17.3 months for epithelioid, 11.4 months for biphasic and 6.4 months for sarcomatoid (p = 0.016).
  • Patients whose tumors did not express PD-L1 had significantly better overall survival (p = 0.041).
  • The median CD4+/regulatory T cell ratio was 1.584 in patients who survived more than 12 months and 0.520 in those with shorter survival (p = 0.015).
  • The median CD4+/regulatory T cell ratio was 1.477 (IQR 0.255 to 6.547) in epithelioid tumors and 0.852 (IQR 0.000 to 2.850) in non-epithelioid tumors (p = 0.017).
  • Patients who survived more than 18 months had a higher median CD4+/CD8+ ratio than those who survived less than 18 months: 27.959 (IQR 21.935 to 40.533) versus 8.991 (IQR 5.654 to 12.977); p less than 0.001.
  • In the multivariate Cox analysis, histological subtype, gender and age were significantly associated with overall survival (p less than 0.001, 0.050 and 0.006). Compared with epithelioid tumors, the hazard ratio was 2.046 (95% CI 1.340 to 3.124) for biphasic and 4.598 (95% CI 1.983 to 10.664) for sarcomatoid tumors.
  • In the multivariate analysis, the CD4+/regulatory T cell ratio remained significantly associated with overall survival: hazard ratio 1.207 (95% CI 1.015 to 1.315), p = 0.044.
  • In the multivariate analysis, the CD4+/CD8+ ratio had a hazard ratio of 0.854 (95% CI 0.724 to 1.006) with p = 0.059. This is above the 0.05 level the authors set for statistical significance, although they described it as continuing to have a strong impact.
• The authors' conclusion: The authors concluded that distinct differences in the T cell immune infiltrates in mesothelioma are strongly associated with overall survival, and that the tumor microenvironment could therefore serve as a source of prognostic biomarkers.
• Limitations the authors state:
  • The study was retrospective.
  • No information on tumor grading was available, because grading of pleural mesothelioma has only recently entered routine practice.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Tumor Microenvironment, Immunotherapy, Overall Survival, Epithelioid, Sarcomatoid, Biphasic Mesothelioma, Non-epithelioid.

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