CD8+ tumor-infiltrating lymphocytes predict favorable prognosis in malignant pleural mesothelioma after resection

Our plain-English summary of CD8+ tumor-infiltrating lymphocytes predict favorable prognosis in malignant pleural mesothelioma after resection, by N. Yamada, S. Oizumi, E. Kikuchi, et al (Cancer Immunology, Immunotherapy, 2010).

The study

• Authors: N. Yamada, S. Oizumi, E. Kikuchi, N. Shinagawa, J. Konishi-Sakakibara, A. Ishimine, K. Aoe, K. Gemba, T. Kishimoto, T. Torigoe, M. Nishimura
• Journal: Cancer Immunology, Immunotherapy
• Published: 2010;59(10):1543-9
• Cited by: 141 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Defects in human leukocyte antigen (HLA) class I expression may allow tumor cells to escape immune recognition. T cell infiltration is associated with a good prognosis in many cancers. However, the role of HLA class I expression and tumor-infiltrating lymphocytes (TILs) in malignant pleural mesothelioma (MPM) has not been fully analyzed. In the present study, we investigated the immune profiles and conducted outcome analyses of MPM patients. HLA class I expression and TILs (CD4(+), CD8(+), and NK cells) were detected by immunohistochemistry in a series of 44 MPM cases. To detect HLA class I expression, specimens were stained with the anti-pan HLA class I monoclonal antibody EMR8-5. The expression of HLA class I was positive in all patients. There was no case that showed negative HLA class I expression. The density of CD4(+) and CD8(+) TILs were strongly correlated (R = 0.76, p < 0.001). A high density of CD8(+) TILs was a significantly better prognostic factor for the survival of patients with extrapleural pneumonectomy (p < 0.05). Multivariate analysis revealed that a high density of CD8(+) TILs is an independent prognostic factor for patients who underwent extrapleural pneumonectomy. The presence of intratumoral CD8(+) T cells was correlated with an improved clinical outcome, raising the possibility that CD8(+) T cells might play a pivotal role in the antitumor immune response against MPMs. Thus, the stimulation of CD8(+) lymphocytes might be an efficacious immunotherapy for MPM patients.

In plain English

This study looked at tumor tissue from 44 patients with malignant pleural mesothelioma diagnosed between May 1997 and January 2008 at four institutes. The authors' affiliations are in Japan. The study did not examine asbestos exposure. Using staining, the authors measured a protein called HLA class I on tumor cells. They also counted CD4+ T cells, CD8+ T cells and CD56+ NK cells inside the tumors. All 44 tumors expressed HLA class I. In 33 patients (75%), 100% of the tumor cells assessed stained positive. Among 35 patients treated with surgery or chemotherapy, survival did not differ significantly by CD8+ cell density. Among the 27 patients who had extrapleural pneumonectomy (surgery), the 13 with a high density of CD8+ cells had significantly longer overall survival than the 14 with a low density. In a multivariate analysis of these surgical patients, high CD8+ density had a hazard ratio of 0.27 (95% CI 0.09 to 0.83) compared with low density. The authors concluded that CD8+ cells may have an important role against the tumor and that stimulating them could be a potential treatment strategy.

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: Laboratory (immunohistochemistry) study of stored tumor specimens, combined with a survival analysis of the patients
• Who was studied: 44 patients with malignant pleural mesothelioma diagnosed between May 1997 and January 2008 at four institutes (author affiliations in Japan). There were 40 men and 4 women, with a median age of 59 (range 35 to 85). Survival was analyzed in 35 patients who had surgery or chemotherapy, and separately in 27 who had surgery.
• Exposure: Not studied. The article reports no asbestos exposure data. It measured immune markers in tumor tissue: HLA class I expression and the density of CD4+, CD8+ and CD56+ (NK) tumor-infiltrating lymphocytes.
• Main results:
  • All patients' tumors expressed HLA class I. Expression was assessed as the percentage of positive tumor cells in at least five high-power microscopic fields. It was 100% in 33 patients (75%), and the lowest level was 70%.
  • The densities of CD4+ and CD8+ cells in the tumors were strongly correlated (R = 0.74, p less than 0.001).
  • Among the 35 patients who had surgery or chemotherapy, there was no significant difference in survival by CD8+ cell density.
  • Among the 27 surgically treated patients, those with a high density of CD8+ cells (13 patients) had significantly longer overall survival than those with a low density (14 patients), p less than 0.05.
  • In the multivariate analysis of patients who had extrapleural pneumonectomy, high CD8+ density was an independent prognostic factor (hazard ratio 0.27, 95% CI 0.09 to 0.83). Epithelioid histology, compared with non-epithelioid, had a hazard ratio of 0.19 (95% CI 0.06 to 0.6).
  • In surgical patients, a high density of CD4+ cells tended toward better survival (p = 0.104), but this was not statistically significant. Density of CD56+ NK cells showed no significant survival difference.
• The authors' conclusion: The authors concluded that CD8+ tumor-infiltrating lymphocytes have an important role in antitumor immunity in mesothelioma patients and that stimulating CD8+ lymphocytes can be a potential therapeutic strategy.
• Limitations the authors state:
  • The study did not evaluate activation markers of CD8+ T cells or the subtypes of CD4+ T cells (such as regulatory T cells).

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Tumor-Infiltrating Lymphocytes, Prognosis, Pleural Mesothelioma, Immunohistochemistry, Monoclonal Antibody, Extrapleural Pneumonectomy (EPP), Multivariate Analysis, Immunotherapy.

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