Tumor infiltrating lymphocytes (TILs) before and after neoadjuvant chemoradiotherapy and its clinical utility for rectal cancer

Am J Cancer Res. 2015 May 15;5(6):2064-74. eCollection 2015.


Backgrounds: Radiotherapy (RT) and chemotherapy (CT) can potentiate systemic antitumor immune effect. However, immunomodulation during RT or CT and their clinical implications in rectal cancer have not been thoroughly investigated.

Methods: We investigated alterations in the densities of tumor infiltrating lymphocytes (TILs) during chemoradiation and their clinical utilities in patients with rectal cancer. We analyzed 136 rectal cancer patients who underwent neoadjuvant RT, CT or chemoradiotherapy (CRT), followed by radical resection retrospectively. Pretreatment biopsy specimens and posttreatment resected specimens of all patients were immunostained for CD3 and CD8. The predictive value of TILs to neoadjuvant treatment and prognosis were examined.

Results: Densities of CD3+ and CD8+TILs in posttreatment specimens after RT, CT or CRT were all significantly higher than those in pretreatment specimens. There were no significant differences between each two of these three groups. High pretreatment CD3+ and CD8+TILs were associated with good response (TRG ≥ 3) after neoadjuvant treatments (P = 0.033 and 0.021). High CD3+TILs and CD8+TILs in pretreatment biopsy specimens were significantly associated with favorable disease free survival (DFS) (P = 0.010 and P = 0.022) and overall survival (OS) (P = 0.019 and P = 0.003).

Conclusions: We may, thus, conclude that chemoradiation can enhance local immune response by increased TILs. High TILs densities before treatment are associated with good response to neoadjuvant chemoradiotherapy and a favorable prognosis.

Keywords: Rectal cancer; chemoradiotherapy; inflammation; lymphocytes; prognosis.