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

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.

Fig. 1

Representative images of immunohistochemical staining of a 100% positive expression of HLA class I, cell membranes of tumor cells are completely stained; b 70% positive expression of HLA class I; c anti-CD4 antibody; d anti-CD8 antibody; and e anti-CD56 antibody (scale bar 50 μm)

Fig. 2

Histogram of percentage of HLA class I expression; 100% of HLA class I expression in 33 patients (75%), 95% in 6 patients (14%), 90% in 2 patients (4%), 80% in 1 patient (2%), and 70% in 2 patients (4%)

Fig. 3

Kaplan–Meier curves show overall survival after treatment (extrapleural pneumonectomy or chemotherapy) according to the density of CD8⁺ TILs (a), and overall survival after extrapleural pneumonectomy according to the density of CD8⁺ TILs (b)