Target Discovery and Validation Reviews and Protocols

300 Sioud
tumor infiltrating lymphocyte supports the activation of these T-cells by tumor
antigens (4,5). Indeed, specific homing of T-cells into tumor tissues compared
with the surrounding normal tissues was found (5). The existence of immune
response against tumors has now been validated in several studies (see
Chapter 1–15, Volume 1). However, in contrast to the notion that the immune
system should eliminate tumor cells, the developed responses failed to prevent
tumor growth. According to the current view, the immune system also
functions to select tumor variants with reduced immunogenicity capable of
withstanding the tumor-suppressing activity of the immune response (52).
This process, which is referred to as cancer “immunoediting,” is a dynamic
process composed of at least three phases: elimination, equilibrium, and escape. To
become clinically detectable, cancer cells must circumvent both innate and adaptive
immunity. Thus, the host immunological environment selects tumors during
tumor development and therefore leads to the generation of the selected tumors
that survive with reduced immunogenicity. This heartening truth, which arises
because most of the tumor cells are under constant selection pressure for survival,
has been underlined by several recent studies (52).
11. Technical Advances in Tumor Antigen Discovery
One aim of tumor immunology is to increase the antitumor immune
response and to mediate killing of tumor cells by the host’s immune system,
in particular, Tc cells (53). Given the prevalence of autoantigens on human
cancers and the ability of tumors to induce tolerance to neoantigens acquired
during transformation, tolerance is emerging a central obstacle for immune
recognition of human cancer antigens. Because tumor cells do not express
costimulatory molecules, antigens presented by these cells will induce tolerance
despite being tumor specific. Thus, one of the main challenges of this
field is to identity tumor antigens capable of inducing protective antitumor
immunity as well as to uncover the cellular and molecular mechanisms that
lead to the strange behavior of the immune system toward tumor cells. To
identify tumor antigens, here referred as tumor-associated antigens (TAAs)
and tumor-specific antigens (TSAs), several techniques have been explored.
11.1. Autologous Typing
Autologous typing was an early approach of determining whether patients
with cancer recognize tumor-specific antigens on the surface of their cancer
cells (54). Sera from patients with cancer were tested for reactivity with surface
antigens of cultured autologous cancer cells and normal cells. Positive reactivity
simply signifies that the antigens being detected on the target cells. Because
of the potential presence of alloantibodies directed against alloantigens not
present on other autologous cell types, extensive absorption steps are needed to