|Cancer||Cell death||Cell cycle||Cytoskeleton||Exo/endocytosis||Differentiation||Division||Organelles||Signalling||Stem cells||Trafficking|
Tumour escape mechanisms and their therapeutic implications in combination tumour therapy
Sujit K Bhutia*, Sanjaya K Mallick† and Tapas K Maiti†1
*Department of Life science, National Institute of Technology, Rourkela 769008, Orissa, India, and †Department of Biotechnology, Indian Institute of Technology, Kharagpur 721302, India
Most tumours arise from a single normal cell through a sequential evolutionary process of mutation and selection. Tumours are initiated by escaping non-immune surveillance, which includes defective DNA repair, epigenetic gene alternation, resistance to apoptosis and loss of intercellular contact inhibition. Tumour cells harbour mutations in a number of critical genes that provide selective advantages at various stages during the evolution of the tumour. The tumour cells that circumvent the tumour suppressor mechanisms of the non-immune surveillance process are edited by the immune system, resulting in the selection of a resistant tumour variant. The selection of the tumour cell is further shaped by its interactions with cells and other factors in its microenvironment. Tumour evolution is thought to adhere to Darwinian principles by escaping both non-immune (intrinsic) and immune (extrinsic) responses against self-altered tumour cells. At end-stage, tumours have escaped both non-immune and immune surveillance with increased threshold of apoptosis. Combination therapy has been proposed, by exploring the non-immune and immune suppressive nature of the tumour, and has been found to have a therapeutic efficiency on tumour regression as compared with monotherapies. The combination of immunotherapy and other different modalities, especially vaccines, with conventional anticancer therapies with optimized dosage and scheduling can offer synergistic antitumour effects. Here, we focus on the mechanism of tumour evolution and its implication in combination therapy.
Key words: combination therapy, immune escape, non-immune escape, tumour evolution
Abbreviations: APC, antigen-presenting cell, ARG, arginase, CEA, carcinoembryonic antigen, CTL, cytotoxic T lymphocyte, CTLA4, CTL antigen 4, DAMP, damage-associated molecular-pattern, DC, dendrite cell, FGF, fibroblast growth factor, 5-FU, 5-fluorouracil, GM-CSF, granulocyte macrophage colony-stimulating factor, HAT, histone acetyltransferase, HDAC, histone deacetylase, IDO, indoleamine 2,3-dioxygenase, IFN-γ, interferon-γ, IGF2, insulin-like growth factor-2, IL, interleukin, mAb, monoclonal antibody, MMR, mismatch repair, MSC, myeloid suppressor cell, NK, natural killer, pRb, retinoblastoma protein, PSA, prostrate-specific antigen, Sm-153, samarium-153, TAM, tumour-associated macrophage, TGF-β, transforming growth factor-β, TNF-α, tumour necrosis factor-α, TRAIL, TNF-related apoptosis-inducing ligand, Treg cell, regulatory T-cell, VEGF, vascular endothelial growth factor, VEGFR, VEGF receptor, XP, xeroderma pigmentosum
1To whom correspondence should be addressed (email firstname.lastname@example.org or email@example.com).
Received 13 September 2009/10 February 2010; accepted 25 February 2010
Published online 8 April 2010, doi:10.1042/CBI20090206
© The Author(s) Journal compilation © 2010 Portland Press Limited