Tumor-infiltrating lymphocytes, forkhead box P3, programmed death ligand-1, and cytotoxic T lymphocyte–associated antigen-4 expressions before and after neoadjuvant chemoradiation in rectal cancer

摘要: Preclinical studies have suggested that cytotoxic agents and radiation may partly deliver their antitumor activities by activating immune response. However, the alterations of tumor microenvironment including immunosuppressive molecules during chemoradiotherapy associations with clinical features prognosis in rectal cancer not been thoroughly investigated. Therefore, we investigate densities cluster differentiation 8 (CD8) positive tumor-infiltrating lymphocytes (TILs), CD4+TILs, natural killer cell (NK)-TILs, myeloid-derived suppressor cells (MDSCs), transcription factor forkhead box P3 (FOXP3)+TILs, programmed death ligand-1 (PD-L1), T lymphocyte-associated antigen-4 (CTLA-4) before after neoadjuvant (nCRT) patients to determine predictive prognostic effects. We screen 62 who underwent nCRT followed radical surgery. Pretreatment biopsy specimens posttreatment surgically resected all are retrieved perform immunohistochemistry CD8, CD4, CD56, FOXP3, CD33, CD11b, PD-L1, CTLA-4. The CD8+TILs CD4+TILs post-nCRT significantly higher than pre-nCRT (P = 0.004 0.005, respectively). Expressions MDSC, FOXP3+TILs, CTLA-4 relative stable nCRT. Tumors high density CD8+TILs, low MDSC-TILs more sensitive 0.022, 0.022 High pretreatment associated better disease-free survival overall 0.016 NK-TILs detected only 6 evaluated. Cell surface PD-L1 (1 62) stroma (3 very low. conclude immunity is activated increased infiltrating CD8+ CD4+ numbers MDSC-TILs, coinhibitory molecules. Pre-nCRT marker for response CRT, prognosis.