There is consensus that cancer cells are antigenic since they express tumor-associated antigens that are recognized by autologous T cells. Several lines of evidence suggest that T cells are the main effectors in the immunological response against cancer cells [
12]. Importantly, many T cell antigens are known to elicit spontaneous reactivity. More than 200 class I-restricted cytotoxic T-lymphocyte (CTL) peptide epitopes have been characterized, from highly diverse groups of proteins, e.g., Muc-1, telomerase, the MAGE proteins, NY-ESO-1, and p53, etc. [
20]. Due to the phenomenon of “immune escape”, in which antigen-negative cancer cells avoid immune recognition, strategies have been developed that conceptually focus on minimizing the risk of immune escape, by specifically targeting proteins that are important for the function, survival and growth of cancer cells [
30]. Thus, it is well established that molecular events lead to the general cancer traits, e.g., the capacity to uncontrolled growth (abnormal cell cycle regulation), resistance to death (apoptosis resistance), the potential to migrate and grow at distant sites (metastasis), the capacity to induce new blood vessels (attract endothelial cells), and also the mechanisms involved in suppression of the immune system by cancer cells (secretion of immune-suppressive mediators), etc. [
14]. The proteins or protein patterns responsible for these characteristics of cancer cells represent ideally suited target structures for therapeutic intervention, including immunological targeting. Importantly, these traits—molecular mechanisms aside—are essential characteristics of all life-threatening cancers, and therapies based on targeting of these characteristics molecularly are therefore broadly applicable to most if not all cancers. Several proteins responsible for or associated with these cancer traits have been characterized, which are targets for immunological recognition e.g., cell division (telomerase [
31], survivin [
4]), resistance to apoptosis (survivin, Bcl-2, Bcl-X(L), and Mcl-1 [
1]), and tumor development (Cyp1B1 [
18]). Recently, heparanase, a protein with metastasis promoting potential was described to be a target for T cells in cancer patients [
29]. Generally, these targets represent broadly applicable vaccination targets in therapeutic vaccinations against cancer. Moreover, although vaccination against these proteins or groups of proteins is in itself a promising new approach to fight cancer, the combination with additional therapy could create a number of synergistic effects.
Rho GTPases affect several aspects of growth control, and cytoskeletal organization in response to extracellular factors [
32]. Three Rho family members exist in humans; RhoA, B and C, which are highly homologous but with extensive heterogeneity in the C-terminal of the sequence. Although RhoB and RhoC were characterized at the same time as RhoA, they have received less attention because of their extensive homology to RhoA and because over-expression studies indicated that, like RhoA, they induced stress fibers in cells. More recent data suggests a more differential role in that RhoC has been shown to play an important role in metastasizing cancer cells [
11]. Thus, several lines of evidence demonstrate a high expression of RhoC in cancer cells, and that the metastatic potential of cancer cells depends on expression of RhoC. Selective increased expression of RhoC has been described in metastatic cancers. Microarray analysis has shown that expression of RhoC is progressively increased as tumors become more aggressively metastatic and RhoC expression promotes metastasis [
23,
33]. It has been demonstrated that loss of RhoC does not affect tumor development but decreases tumor cell motility and metastatic cell survival leading to a drastic inhibition of metastasis [
13]. Interestingly, RhoC has not been found mutated in cancers, indicating that upregulated expression is sufficient to contribute to metastasis. In the present study, we examined whether RhoC is a target for cytotoxic T cells in patients with metastatic cancer.