Correlation between tumor microenvironment-associated factors and the efficacy and prognosis of neoadjuvant therapy for rectal cancer

Oncol Lett. 2019 Jan;17(1):1062-1070. doi: 10.3892/ol.2018.9682. Epub 2018 Nov 9.

Abstract

The tumor microenvironment contributes to the survival and development of tumor cells and is therefore a key target for cancer therapy. The tumor microenvironment has unique physical and chemical properties and is associated with inflammation and immunity. To examine the correlation between tumor microenvironment-associated factors and the efficacy and prognosis of neoadjuvant therapy for rectal cancer, and to compare the differences between two treatments [neoadjuvant chemotherapy (NAC) vs. neoadjuvant chemoradiotherapy (NACR)], an immunohistochemical method was used to measure the expression levels of CD4+ tumor-infiltrating lymphocytes (TILs), cluster of differentiation (CD)8+TILs, forkhead box P3 (FOXP3)+TILs, cytotoxic T lymphocyte-associated antigen-4+TILs and programmed death ligand-1 (PD-L1)+TILs in 109 patients with rectal cancer, pre- and post-neoadjuvant therapy. The significance of these protein expression patterns was also analyzed using tissue microarrays, and the prognostic significance of these findings evaluated. The results indicated that high levels of CD4+TILs, CD8+TILs and PD-L1+TILs may be associated with favorable responses to neoadjuvant therapy, whereas high levels of FOXP3+TILs were associated with poor therapeutic responses. Expression levels of CD8+TILs and FOXP3+TILs following neoadjuvant therapy were independent prognostic factors and affected the total survival of patients subjected to neoadjuvant therapy for the treatment of rectal cancer. Moreover, the effects of NAC and NACR on the tumor microenvironment may be different.

Keywords: neoadjuvant therapy; rectal cancer; tissue microarrays; tumor microenvironment; tumor-infiltrating lymphocytes.