E7 1) 6% in primary versus

43% in metastastic tumors; 2) 0% in G1, 33% in G2 and 67% in G3 [28] Prostate A-072 1) 0% in Benign, 41% Dinaciclib cost in primary and 66% in LN metastases; 2) 33% in low-grade versus 50% in high grade lesions [29] *The cutoff line for negative staining or total loss is 5 to 25% of cells stained with antibodies. W6/32 monoclonal antibody (mAb) detects monomorphic epitope of HLA class I antigen (HLA-ABC); 246-E8.E7, HC-10 and GRH1 are anti-beta2-microglobulin (β2-m) mAbs; rA-270 is rabbit polyclonal anti-β2-m antibody (DAKO). A higher level of HLA class I expression in bladder carcinoma is significantly associated with a longer survival rate in PF299 cost patients [21], and tumors with a normal level of HLA class I harbor more CD8+ T cells than those Crenigacestat solubility dmso with altered HLA class I in renal cell carcinomas (RCC) [30] and cervical carcinoma [31, 32]. In addition, a decrease in HLA class I expression has been noted as early as in normal mucosa surrounding the tumor or in situ lesion, and is significantly associated with subsequent development to a new primary tumor lesion [33, 34]. These data indicate that the avoidance

strategy may occur at early stages of carcinoma development, and suggest that by loss of HLA class I expression to avoid CD8+ CTL seems critical for the development of carcinoma in patients. Heterogeneous expression of HLA class I in inactivation of NK cell cytotoxicity Although loss of HLA class I may benefit to carcinoma resistance to CD8+ CTL as discussed above, it could increase the susceptibility to cytotoxicity of natural killer (NK) cells [35] because HLA class I is a ligand for inhibitory receptor family, killer cell immunoglobulin-like receptor (KIR) of NK cells [36], Thus, loss of HLA class I expression could favor the escape of antigen-dependent cytotoxicity of CD8+ CTL, but at the same time carcinoma cells may become a target of NK cell cytotoxicity. To date, it is not completely clear how carcinoma cells can survive under

the Sclareol selection of both CD8+ CTLs and NK cells simultaneously. It has been suggested that carcinoma cells find a balance between maintenance of HLA class I expression for inhibition of NK cell cytotoxicity and loss of its expression for the escape from CD8+ CTL responses. Indeed, the complete loss of HLA class I is barely seen in carcinomas, which may be explained by its need for inhibition of NK cell activity. The heterogeneous losses of HLA class I either positively or negatively correlate with carcinoma stages or grades in patients [24, 27, 28], reflecting exactly the situation of carcinoma cells; if carcinoma cancer faces more severe cytotoxicity from NK cells versus CD8+ CTL, certain levels of HLA class I render carcinomas resistance to NK cells; if tumor is under the pressure of CD8+ CTL more than NK cells, then partial loss of HLA class I becomes a key for survival, as indicated by Table 1.