**4. Acknowledgment**

This work was supported by Institut National du Cancer, Institut Paoli Calmettes, Institut National de la Santé et de la Recherche Médicale. J. F Z-Z was a Post-doctoral fellow from Universidad Autónoma de Nayarit.

#### **5. References**

424 Advances in Cancer Therapy

Fig. 12. Representative flow cytometry pattern of a selected clone tested on C91T3.3 cells. A) Basal fluorescence; B) Normal binding of CD277-Fc fusion protein; and C) Inhibitory test showing a reduction in the CD277-Fc binding. The percentage of positive cells is indicated

**2.7 Perspectives on the potential use of CD277 and its counter-receptor in cancer** 

The wide variety of function of CD277 described in this chapter shown the future potential of the use of mAbs anti-CD277 to regulate the immune response against tumor cells. The fact that stimulation of different cells by CD277 lead to the secretion of different cytokines, activation of different signalling pathways, enhance the proliferation of T cells, can be useful to modulate the immune response against tumor cells. Moreover, our results showing that Raji cells stimulated by CD277 are better killed by γ T cells are potentially useful for cancer therapy. However, it is necessary to elucidate the mechanisms by which these molecules act and to identify the counter-receptor for CD277. The use of mAbs should be a tool to elucidate the mechanisms, but to be used no to mark the tumor cells, but to modulate the response that

In the near future, regulation of the expression or activity of molecules such as CD277 or its counter-receptor can be useful for enhance the anti-tumoral immune response, however it is necessary the molecular and fully functional characterization of these molecules, and the mechanisms involved in the observed functions, to be used as modulators of immune

Immune responses can be regulated by CD277 in different ways. CD277 affects different immune cells in various ways including inhibition of proliferation, regulation of cytokine secretion in CD4+ and CD8+ T cells, as well as activating monocytes and iDC. Moreover, CD277 promotes the expression of its counter-receptor and this effect may be important for

Proteomics and production and use of monoclonal antibodies are two different approaches we have tested to determine the identity of the CD277 counter-receptor.. However, although functional analysis of CD277 and its counter-receptor has demonstrated a biological effect, it is necessary to identify the counter-receptor and elucidate the signalling pathways involved

in each pattern.

lead to kill them.

response in cancer.

**3. Conclusion** 

in the observed response.

recognition of leukaemia and solid tumor cells.

**therapy** 


**20**

 *China* 

**Transcription Regulation and Epigenetic** 

Throughout the life of an individual organism, a successful host defense relies on the coordination of innate and adaptive immunity (McQueen and Parham, 2002). Natural killer (NK) cells are characteristic cytolytic cells that are integral components of innate immunity and play a major role both in the direct destruction of infected or transformed cells and in the production of cytokines and chemokines that mediate inflammatory responses and exert a regulatory effect on the adaptive immune responses (McQueen and Parham, 2002; Moretta et al., 2006). Cells become susceptible to NK cell-mediated killing following downregulation of cell surface MHC class I expression after virus infection, which ultimately leads to escape from the MHC-restricted adaptive immune system; a phenomenon also seen in metastasized tumor cells. MHC class I-specific NK receptors (NKR) have acquired the ability to detect immune escape variants and in rodents and primates can be grouped into two distinct classes of MHC class I-specific receptor families based on protein structure: the C-type lectin superfamily (Cl-SF) and the immunoglobulin superfamily (Ig-SF). Humans possess a large family of killer cell immunoglobulin-like receptors (KIR) that belong to the Ig superfamily, whereas mice express lectin-like Ly49 receptors that are now not present in humans, except for a single nonfunctional gene fragment (Lanier, 1998, 2001; Vilches and Parham, 2002; Takei et al., 2001). A third family of NKR, the lectin-like CD94/NKG2 heterodimers, are structurally and functionally conserved between rodents and primates and interact with their ligands: nonclassical MHC class I molecules and some specific ligands that are differentially expressed in different tissues in response to different stresses (McQueen and Parham, 2002; Moretta et al., 2006; Raulet et al., 2001; Uhrberg et al., 1997; Valiante et al., 1997). The actions of NK cells, therefore, are thought to be mediated by the complex interactions between inhibitory and activating signals sent by cell-surface receptors

Malignant cells in tumor growth frequently demonstrate alterations in MHC class I expression that play a major role in their ability to escape immune recognition and killing (Dunn et al., 2002; Campoli et al., 2005). NK cells enhance their cytotoxic function and immune regulation by using their stimulatory and inhibitory receptors to maintain the constant balance in the immune system (Chang and Ferrone, 2006). There are major

following ligation (Lanier, 2005; Ravetch and Lanier, 2000).

**1. Introduction** 

**Control of Expression of Natural Killer** 

**Cell Receptors and Their Ligands** 

*Institute of Immunopharmacology & Immunotherapy, School of Pharmaceutical Sciences, Shandong University* 

Zhixia Zhou, Cai Zhang, Jian Zhang and Zhigang Tian

