214
documented as a key element in controlling cellular processes. Any variation in the
composition of the ECM by altered processing, secretion, or expression contrib-
utes greatly to tumorigenesis (Ziober et al. 2006 ). In oral carcinoma, alterations in
cell–cell and cell–extracellular matrix interactions regulate invasion of malignant
cells into the underlying connective tissue and migration of malignant cells to form
metastases at distant sites (Lyons and Jones 2007 ). The major ECM molecules
involved in oral cancer development and progression include fibronectin, laminin
and collagens and their ECM receptors and integrins (α 2 β1, α 3 β1, α 5 β1, and α 6 β4)
(Ziober et al. 2006 ). An immunohistochemical study of extracellular matrix, deco-
rin and vitronectin in OSCC proposes that in primary tumors of metastatic cases,
the expression of laminin, type IV collagen, heparansulphate proteoglycan, deco-
rin and vitronectin obviously decreased, while the expression of fibronectin and
tenascin increased when compared with those of the non-metastatic cases (Harada
et al. 1994 ). The neo-expressed Tenascin-C and one of its integrin receptors
αvβ6 in oral SCC and tumor stromal environment influences the oral SCC behavior
(Ramos et al. 1997 ).
11.4.2 Infiltrating Immune Cells
The host-tumor immune response is extremely complex, multifactorial and dynamic.
Though the primary function of immune system is to destroy the foreign cells;
tumor cells within the tumor microenvironment escape the immune surveillance not
due to the absence of immune cells, but due their aberrant activity. Tumors exploit
the host response by creating a favorable microenvironment during cancer progres-
sion by scheming chronic inflammation to establish a habitat that favor tumor sur-
vival and growth (Whiteside 2006a). Moreover, it is reported that established tumors
have the ability to lessen the immune response and also they are relatively poor in
initiating an immune response (Whiteside 2006b). Therefore, understanding the
immune response within tumor microenvironment holds great importance in tumor
biology. The adaptive immune response contributes in a variety of ways to tumori-
genesis through the immune interactions in the TME. According to reports a hetero-
geneous distribution of tumor infiltrating leucocytes were seen in solid tumor
microenvironment which includes granulocytes, mast cells, macrophages, myeloid-
suppressor cells, natural killer (NK) cells, CD8+ T-cells (CTL), T-memory cells,
T-regulatory (T-reg) cells and dendritic cells (DC) (Fridman et al. 2012 ; Senovilla
et al. 2012 ). The creation of an immune suppressed microenvironment and evasion
of the adaptive immune response may be executed through decreased expression of
major histocompatibility complexes (MHC I) or induction of T cell apoptosis
(Young 2006 ; Ogino et al. 2006 ; Grandis et al. 2000 ). In head and neck cancer, a
reduced expression of MHC-I is reported which is mediated by the overexpression
of gangliosides in tumor cells (Tourkova et al. 2005 ). Moreover, it is reported that
oral carcinoma cells contain membranous FasL-positive vesicles which triggers
T-cell apoptosis induction that helps in evading the cytotoxic response (Young
P.P. Naik et al.