Immune responses and immunotherapeutic interventions in malignant pleural mesothelioma

Division of Thoracic Surgery, Memorial Sloan-Kettering Cancer Center, NY 10065, USA.
Cancer Immunology and Immunotherapy (Impact Factor: 3.94). 09/2011; 60(11):1509-27. DOI: 10.1007/s00262-011-1103-6
Source: PubMed


Malignant pleural mesothelioma (MPM) is an aggressive, primary pleural malignancy with poor prognosis, hypothesized to originate from a chronic inflammatory state within the pleura. Similar to what has been observed in other solid tumors (melanoma, ovarian and colorectal cancer), clinical and pre-clinical MPM investigations have correlated anti-tumor immune responses with improved survival. As such, a better understanding of the complex MPM tumor microenvironment is imperative in strategizing successful immunotherapies. Herein, we review the immune responses vital to the development and progression of MPM, as well as assess the role of immunomodulatory therapies, highlighting recent pre-clinical and clinical immunotherapy investigations.

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    ABSTRACT: Treatment options for malignant mesothelioma are limited, and the results with conventional therapies have been rather disappointing to this date. Chemotherapy is the only evidence-based treatment for mesothelioma patients in good clinical condition, with an increase in median survival of only 2 months. Therefore, there is urgent need for a different approach to battle this malignancy. As chronic inflammation precedes mesothelioma, the immune system plays a key role in the initiation of this type of tumour. Also, many immunological cell types can be found within the tumour at different stages of the disease. However, mesothelioma cells can evade the surveillance capacity of the immune system. They build a protective tumour microenvironment to harness themselves against the immune system's attacks, in which they even abuse immune cells to act against the antitumour immune response. In our opinion, modulating the immune system simultaneously with the targeting of mesothelioma tumour cells might prove to be a superior treatment. However, this strategy is challenging since the tumour microenvironment possesses numerous forms of defence strategies. In this paper, we will discuss the interplay between immunological cells that can either inhibit or stimulate tumour growth and the challenges associated with immunotherapy. We will provide possible strategies and discuss opportunities to overcome these problems.
    Clinical and Developmental Immunology 06/2012; 2012:927240. DOI:10.1155/2012/927240 · 2.93 Impact Factor
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    ABSTRACT: Mesothelioma is a rare thoracic malignancy with a dismal prognosis. Current treatment options are scarce and clinical outcomes are rather disappointing. Due to the immunogenic nature of mesothelioma, several studies have investigated immunotherapeutic strategies to improve the prognosis of patients with mesothelioma. In the last decade, progress in knowledge of the modulation of the immune system to attack the tumor has been remarkable, but the optimal strategy for immunotherapy has yet to be unraveled. Because of their potent antigen-presenting capacity, dendritic cells are acknowledged as a promising agent in immunotherapeutic approaches in a number of malignancies. This review gives an update and provides a future perspective in which immunotherapy may improve the outcome of mesothelioma therapy.
    Immunotherapy 10/2012; 4(10):1011-1022. DOI:10.2217/imt.12.108 · 2.07 Impact Factor
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    ABSTRACT: Malignant pleural mesothelioma (MPM) is an aggressive form of cancer arising from the pleural mesothelium. Trimodality therapy (TMT) involving extrapleural pneumonectomy with neoadjuvant or adjuvant chemotherapy and adjuvant radiotherapy is a recognized treatment option with a curative intent. Despite encouraging results from institutional studies, TMT in the treatment of MPM remains controversial. The present systematic review aims to assess the safety and efficacy of TMT in the current literature. A systematic review was performed using five electronic databases from 1 January 1985 to 1 October 2012. Studies were selected independently by two reviewers according to predefined selection criteria. The primary endpoint was overall survival. Secondary endpoints included disease-free survival, disease recurrence, perioperative morbidity and length of stay. Sixteen studies were included for quantitative assessment, including one randomized controlled trial and five prospective series. Median overall survival ranged from 12.8-46.9 months. Disease-free survival ranged from 10-16.3 months. Perioperative mortality ranged from 0-12.5%. Overall perioperative morbidity ranged from 50-82.6% and the average length of stay was 9-14 days. Outcomes of patients who underwent TMT in the current literature appeared to be inconsistent. Four prospective series involving a standardised treatment regimen with neoadjuvant chemotherapy indicated encouraging results based on intention-to-treat analysis. However, a small study assessing the feasibility of conducting a randomized controlled trial for TMT versus conservative treatment reported poor short- and long-term outcomes for patients who underwent pneumonectomy. Overall, results of the present systematic review suggest TMT may offer acceptable perioperative outcomes and long-term survival in selected patients treated in specialized centers.
    11/2012; 1(4):428-37. DOI:10.3978/j.issn.2225-319X.2012.11.07
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