Immunogenic anti-cancer chemotherapy as an emerging concept

• Published in: Current opinion in immunology Vol. 20; no. 5; pp. 545 - 557
• Main Authors: Haynes, Nicole M, van der Most, Robbert G, Lake, Richard A, Smyth, Mark J
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2008
• Subjects: Allergy and Immunology; Animals; Antigens, Neoplasm - immunology; Antigens, Neoplasm - metabolism; Antineoplastic Agents - therapeutic use; Apoptosis - immunology; Combined Modality Therapy; Cytokines - immunology; Cytokines - metabolism; Dendritic Cells - immunology; Dendritic Cells - metabolism; Humans; Immunologic Factors - therapeutic use; Immunotherapy; Neoplasms - drug therapy; Neoplasms - immunology; Receptors, Pattern Recognition - immunology; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - metabolism
• ISSN: 0952-7915; 1879-0372
• DOI: 10.1016/j.coi.2008.05.008

Tumors can acquire mutations or hijack regulatory pathways of the host immune system to render them resistant to immune attack. Standard first line therapies such as chemotherapy and radiation were not thought to provoke natural immunity to cancer, but recent findings demonstrating that dying tumor cells present and release key signals to stimulate or evade neighboring leukocytes are challenging that view. Killing tumor cells in a manner that provides danger signals and tumor antigens in the right context promotes the engagement of innate and adaptive immunity; however, this response alone will not be effective against established cancer. Coincidently driving the immune response with specific monoclonal antibodies and other immunomodulators that activate and mature dendritic cells and co-stimulate T cells and other lymphocytes is one approach. Additionally releasing immune checkpoints and inhibiting tumor-derived molecules that prevent effective tumor immunity is another. Combined these approaches have enormous potential to improve the current outcomes from conventional cancer therapy.