Treatment with interleukin-2 in malignant pleural mesothelioma: immunological and angiogenetic assessment and prognostic impact.
BACKGROUND
Administration of interleukin-2 (IL-2) has shown some effects on malignant pleural mesothelioma (MPM) tumour regression. The purpose of this study was to investigate the ability of IL-2 to modify immunological effector cells and angiogenesis in MPM patients and their prognostic value.


METHODS
Tumour-infiltrating lymphocytes (CD4, CD8, Foxp3), mast cells (MCs) (tryptase and chymase), microvessel count (MVC) and VEGF were determined by immunohistochemistry in two series of MPM patients: 60 patients treated with intra-pleural preoperative IL-2 and 33 patients untreated.


RESULTS
Tryptase MCs, and CD8 and Foxp3 lymphocytes were significantly increased in the IL-2-treated group, whereas MVC was significantly lower in the same group. Moreover, in the IL-2-treated group, greater tryptase+MCs and greater Foxp3 lymphocytes were associated with improved and poorer clinical outcomes, respectively. Notably, when these two immunological parameters were combined, they predicted outcomes more effectively.


CONCLUSIONS
This study showed that IL-2 treatment leads to a significant increase of immunological parameters, concomitantly with a reduction in vasculature, providing new insight into the cancer mechanisms mediated by IL-2. Moreover, these results suggest that tryptase-positive MCs and Foxp3+ lymphocytes predict clinical outcomes in IL-2-treated patients, highlighting the critical role of the inflammatory response in mesothelioma cancer progression.
Alì
G
G
Division of Pathological Anatomy, Department of Surgery, University of Pisa, Via Roma 57, Pisa 56126, Italy.
Boldrini
L
L
Lucchi
M
M
Picchi
A
A
Dell'Omodarme
M
M
Prati
M C
MC
Mussi
A
A
Corsi
V
V
Fontanini
G
G
D000328:Adult; D000368:Aged; D018450:Disease Progression; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007376:Interleukin-2 / Q000276:immunology / Q000627:therapeutic use*; D008214:Lymphocytes / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000276:immunology; D008654:Mesothelioma / Q000098:blood supply / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008875:Middle Aged; D015999:Multivariate Analysis; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000276:immunology; D010997:Pleural Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D011379:Prognosis; D015996:Survival Rate; D016896:Treatment Outcome; D053802:Tryptases / Q000276:immunology
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007376:Interleukin-2; D053802:Tryptases