Article

Escape strategies and reasons for failure in the interaction between tumour cells and the immune system: how can we tilt the balance towards immune-mediated cancer control?

Istituto Nazionale Tumori, ViaVenezian 1, 20133 Milan, Italy.
Expert opinion on biological therapy (Impact Factor: 3.65). 05/2005; 5(4):463-76. DOI: 10.1517/14712598.5.4.463
Source: PubMed

ABSTRACT The last decade has witnessed an exponential increase in the attempts to demonstrate that adaptive immunity can effectively detect cancer cells and impair their growth in vivo in cancer patients. However, clinical trials of immunotherapy with a broad array of immunisation strategies have depicted a rather disappointing scenario, suggesting that successful control of tumour growth by immunotherapeutic treatments may not be an easy task to achieve. The attention of tumour immunologists has thus been switched to the potential reasons of failure, and extensive efforts are being made in defining the cellular and molecular pathways interfering with the capacity of the immune system to develop powerful immunological reactions against tumour cells. Although many of these pathways have been well characterised in murine models, little and controversial information about their role in determining neoplastic progression in cancer patients is available. This discrepancy at the moment represents one of the major limitations in understanding the obstacles to the in vivo development of protective T cell-mediated immune responses against tumours, and how pharmacological or biological interventions aimed at bypassing tumour escape mechanisms would indeed result in a clinical benefit. The study of the reasons for the failure of the immune system to control tumour growth, which have to be ascribed to highly interconnected phenomena occurring at both tumour and immune levels, could in the near future provide adequate tools to fight cancer by finely tuning the host environment through biological therapies.

0 Followers
 · 
67 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Immunotherapy for the treatment of breast cancer can be categorized as either (a) specific stimulation of the immune system by active immunization, with cancer vaccines, or (b) passive immunization, such as tumor-specific antibodies (including immune modulators) or adoptive cell therapy that inhibit the function of, or directly kill, tumor cells. We will present the current information and the future perspectives of immunotherapy in patients with breast cancer, including the prognostic role of tumor infiltrating lymphocytes, immune signatures, targeted therapies modulating the immune system, and tumor antigen cancer vaccines. Active immunotherapy in breast cancer and its implementation into clinical trials have been largely a frustrating experience in the last decades. The concept that the immune system regulates cancer development is experiencing a new era of interest. It is clear that the cancer immunosurveillance process indeed exists and potentially acts as an extrinsic tumor suppressor. Also, the immune system can facilitate tumor progression by sculpting the immunogenic phenotype of tumors as they develop. Cancer immunoediting represents a refinement of the cancer immunosurveillance hypothesis and resumes the complex interaction between tumor and immune system into three phases: elimination, equilibrium, and escape. Major topics in the field of immunology deserve a response: what do we know about tumor immunogenicity, and how might we therapeutically improve tumor immunogenicity? How can we modulate response of the immune system? Is there any gene signature predictive of response to immune modulators? The success of future immunotherapy strategies will depend on the identification of additional immunogenic antigens that can serve as the best tumor-rejection targets. Therapeutic success will depend on developing the best antigen delivery systems and on the elucidation of the entire network of immune signaling pathways that regulate immune responses in the tumor microenvironment.
    Breast Cancer Research 02/2014; 16(1):204. DOI:10.1186/bcr3620 · 5.33 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Melanoma is known for its rapid progression, metastasis to distant organs and therapeutic resistance. Despite high melanoma immunogenicity, the results of immunotherapeutic clinical studies are mostly unsatisfactory. One explanation is the development of strong immunosuppression mediated by highly immunosuppressive regulatory leukocytes, in particular, myeloid-derived suppressor cells (MDSCs). These cells were found to be enriched and activated in the melanoma microenvironment, inducing a profound impairment of anti-tumor immune responses and leading to the tumor progression. Therefore, understanding the mechanisms of MDSC generation, migration to the tumor site and activation as well as their targeting is important for the development of novel strategies for effective melanoma immunotherapy. We suggest that such therapeutic approaches should involve the inhibition of MDSC-mediated immunosuppressive melanoma microenvironment combined with other immunologic treatments.
    Journal der Deutschen Dermatologischen Gesellschaft 09/2014; 12(11). DOI:10.1111/ddg.12411 · 1.40 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cancer vaccine development efforts have recently gained momentum, but most vaccines showing clinical impact in human trials tend to be based on technology approaches that are very costly and difficult to produce at scale. With the projected doubling of the incidence of cancer and its related cost of care in the U.S. over the next two decades, the widespread clinical use of such vaccines will prove difficult to justify. Heat shock protein-based vaccines have shown the potential to elicit clinically meaningful immunologic responses in cancer, but the predominant development approach – heat shock protein–peptide complexes derived from a patient’s own tumor – face similar challenges of cost and scalability. New innovative modalities for deploying heat shock proteins in cancer vaccines may open the door to vaccines that can generate potent cytotoxic responses against multiple tumor targets and can be made in a cost-effective and scalable manner.
    Expert Review of Vaccines 12/2014; 14(3). DOI:10.1586/14760584.2015.979797 · 4.22 Impact Factor