Toll-like receptor (TLR) activation may be an important event in tumor cell immune evasion. TLR2 and TLR4 gene polymorphisms correlate with increased susceptibility to cancer development, response to conventional chemotherapy in various organs.
Treatment results of 62 patients with breast cancer stages T1-3N0-3M0 treated with neoadjuvant chemotherapy were evaluated. The level of the post-treatment CD4+, CD8+, FOP3+ tumor-infiltrating immune cells and Ki-67 positive cells were studied. The polymorphisms of TLR4 (C399T) and TLR2 (G753A) genes were investigated using a PCR restriction fragment length polymorphism method. Statistica10.0 software was used to perform analysis of variance.
ER+ and PR± expressing tumors were identified in 69.3% of patients, ER and PR negative tumors - in 30.6%. Pathological complete response (pCR) was identified in 14.6%. Genotype CC of TLR4 (C399T) gene was detected in 87%, whereas genotype CT - in 9.6% and genotype TT - in 3.4% of patients. Genotype GG of TLR2 (G753A) gene was detected in 88.7%, genotype GA - in 11.3% of patients. A correlation was found between polymorphisms of TLR2 (G753A) and axillary lymph nodes involvement. In carriers of GA genotype of TLR2 gene (G753A) we found more frequent axillary LN metastases (χ2=5.75; p = 0.01). A direct correlation was identified between level of Ki-67 and the level of regulatory FOXP3 cells in carriers of GA genotype of TLR2 gene(r = 0.96; p = 0.008). There appears to be a relationship between TLR4 gene and levels of CD4 + (p=0.01) and CD8 + (p=0.02) as well as an association between TLR4 (C399T) gene and residual cancer burden (RCB) (p = 0.04). In carriers of TT genotype of TLR4 gene the level of CD4+ cells was significantly lower (p = 0.03). In carriers of CC genotype of TLR4 (C399T) gene we found a direct correlation between the level of CD8+ cells and Ki- 67 in the residual tumor (r = 0.38, p = 0.01). Higher level of CD4+ is associated with lower RCB in carriers of CC genotype of TLR4 (C399T) gene (r = 0.3, p
Preliminary results of the study indicate that further elucidation of the role of the TLRs in breast cancer development is promising.
Clinical trial identification
Legal entity responsible for the study
National Cancer Institute
National cancer institute
All authors have declared no conflicts of interest.