Impact of tumor-infiltrating T cells on survival in patients with malignant pleural mesothelioma.
OBJECTIVE
The aim of the study was to determine the impact of tumor-infiltrating lymphocytes on survival in patients with malignant pleural mesothelioma treated with induction chemotherapy followed by extrapleural pneumonectomy.


METHODS
We performed an immunohistochemical analysis of 32 extrapleural pneumonectomy specimens to assess the distribution of T-cell subtypes (CD3(+), CD4(+), and CD8(+)), regulatory subtypes (CD25(+) and FOXP3(+)), and memory subtype (CD45RO(+)) within the tumor.


RESULTS
Patients with high levels of CD8(+) tumor-infiltrating lymphocytes demonstrated better survival than those with low levels (3-year survival: 83% vs 28%; P = .06). Moreover, high levels of CD8(+) tumor-infiltrating lymphocytes were associated with a lower incidence of mediastinal node disease (P = .004) and longer progression-free survival (P = .05). Higher levels of CD8(+) tumor-infiltrating lymphocytes were observed in patients treated with cisplatin and pemetrexed than in those treated with cisplatin and vinorelbine (P = .02). Patients presenting high levels of CD4(+) or CD25(+) tumor-infiltrating lymphocytes or low levels of CD45RO(+) also demonstrated a trend toward shorter survival. However, the presence of FOXP3(+) tumor-infiltrating lymphocytes did not affect survival. After multivariate adjustment, high levels of CD8(+) tumor-infiltrating lymphocytes remained an independent prognostic factor associated with delayed recurrence (hazard ratio = 0.38; confidence interval = 0.09-0.87; P = .02) and better survival (hazard ratio = 0.39; confidence interval = 0.09-0.89; P = .02).


CONCLUSIONS
The presence of high levels of CD8(+) tumor-infiltrating lymphocytes is associated with better prognosis in patients undergoing extrapleural pneumonectomy for malignant pleural mesothelioma. The stimulation of CD8(+) lymphocytes can be a potential therapeutic strategy to improve outcome.
Anraku
Masaki
M
Division of Thoracic Surgery, Toronto General Hospital, University Health Network, University of Toronto, Ontario, Canada.
Cunningham
Kristopher S
KS
Yun
Zhihong
Z
Tsao
Ming-Sound
MS
Zhang
Li
L
Keshavjee
Shaf
S
Johnston
Michael R
MR
de Perrot
Marc
M
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008654:Mesothelioma / Q000276:immunology / Q000628:therapy*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D010997:Pleural Neoplasms / Q000276:immunology / Q000628:therapy*; D011013:Pneumonectomy; D011379:Prognosis; D016019:Survival Analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000970:Antineoplastic Agents