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Abstract: In this paper we present a travelling-wave analysis of a mathematical model describing the growth of a solid tumour in the presence of an immune system response. From a modelling perspective, attention is focused upon the attack of tumour cells by tumour infiltrating cytotoxic lymphocytes (TICLs), in a small multicellular tumour, without necrosis and at some stage prior to (tumour-induced) angiogenesis. As we have shown in previous work, for a particular choice of parameters, the underlying reaction–diffusion–chemotaxis system of partial differential equations is able to simulate the well-documented phenomenon of cancer dormancy by depicting spatially heterogeneous tumour cell distributions that are characterized by a relatively small total number of tumour cells. This behaviour is consistent with several immunomorphological investigations. Moreover, the alteration of certain parameters of the model is enough to induce bifurcations into the system, which in turn result in tumour invasion in the form of a standard travelling wave. The work presented in this paper complements the bifurcation analysis undertaken by Matzavinos et al. [Math. Med. Biol. IMA 21 (2004) 1–34] and establishes the existence of travelling-wave solutions for the system under discussion by promoting the understanding of the geometry of an appropriate phase space. To cite this article: A. Matzavinos, M.A.J. Chaplain, C. R. Biologies 327 (2004). [Copyright &y& Elsevier]

Innate and adaptive immune responses have many interactions that are regulated by the balance of signals initiated by a variety of activatory and inhibitory receptors. Among these, the NKG2D molecule was identified as expressed by T lymphocytes, including most CD8+ cells and a minority of CD4+ cells, designated TNK cells in this paper. Tumor cells may overexpress the stress-inducible NKG2D ligands (NKG2DLs: MICA/B, ULBPs) and the NKG2D signaling has been shown to be involved in lymphocyte-mediated anti-tumor activity. Aberrant expression of NKG2DLs by cancer cells, such as the release of soluble form of NKG2DLs, can lead to the impairment of these immune responses. Here, we discuss the significance of NKG2D in TNK-mediated anti-tumor activity. Our studies demonstrate that NKG2D+ T cells (TNK) are commonly recruited at the tumor site in melanoma patients where they may exert anti-tumor activity by engaging both TCR and NKG2D. Moreover, NKG2D and TCR triggering was also observed by peripheral blood derived T lymphocyte- or T cell clone-mediated tumor recognition, both in melanoma and colorectal cancer (CRC) patients. Notably, heterogeneous expression of NKG2DLs was found in melanoma and CRC cells, with a decrease of these molecules along with tumor progression. Therefore, through the mechanisms that govern NKG2D engagement in anti-tumor activity and the expression of NKG2DLs by tumor cells that still need to be dissected, we showed that NKG2D expressing TNK cells are a relevant T cell subtype for immunosurveillance of tumors and we propose that new immunotherapeutic interventions for cancer patients should be aimed also at enhancing NKG2DLs expression by tumor cells. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, we focus our attention on the relevance of HLA-G in cancer in the light of our recent advances on the expression and immunological function of HLA-G. Regarding HLA-G function, we recently showed that in addition to its direct inhibitory effects on T, APC and NK function, HLA-G induces suppressor cells via two distinct processes: (i) either by cell differentiation of naïve T cells into lasting suppressor T cells or (ii) by rapid transfer of HLA-G from APC or tumor cells to T or NK cells converting them into temporary HLA-G-positive suppressor cells. Regarding HLA-G expression, we described that tumor-microenvironment factors such as hypoxia, IDO and, TNF-α regulate the expression of HLA-G by tumor cells in a way that favors tumor escape from NK lysis. These findings reinforce the role of HLA-G as one mechanism of tumor-driven immune evasion and provide potential targets for testing novel anticancer treatment strategies. [Copyright &y& Elsevier]