Significance of tumor‐infiltrating lymphocytes before and after neoadjuvant therapy for rectal cancer

Abstract

Neoadjuvant therapy for locally advanced rectal cancer is becoming increasingly common. However, biomarkers predicting the response to neoadjuvant therapy have not been established. Tumor‐infiltrating lymphocytes (TILs) have a crucial effect on tumor progression and survival outcome as the primary host immune response, and an antitumor immune effect has been reported to contribute to the response to radiotherapy and chemotherapy. We investigated the significance of TILs before and after neoadjuvant treatment and the change in the density of those TILs. Sixty‐four patients who underwent radical resection after neoadjuvant treatment for locally advanced rectal cancer were enrolled. The number of TIL subsets was examined using immunohistochemical staining of pretreatment biopsy samples and post‐treatment resected specimens. In both the neoadjuvant chemotherapy cohort and the neoadjuvant chemoradiotherapy cohort, a low density of CD8+ TILs in pretreatment biopsy samples was associated with a poor response, and a low density of CD8+ TILs in post‐treatment resected specimens was similarly associated with a poor response. In the neoadjuvant chemoradiotherapy cohort, the density of CD8+ TILs in post‐treatment resected specimens was significantly increased compared with that in pretreatment biopsy samples. We concluded that T lymphocyte‐mediated immune reactions play an important role in tumor response to neoadjuvant treatment for rectal cancer, and the evaluation of TILs in pretreatment biopsy samples might be a predictor of the clinical effectiveness of neoadjuvant treatment. Furthermore, neoadjuvant therapy, especially chemoradiotherapy, could induce the activation of the local immune status.

Association of TIM-3 with BCLC Stage, Serum PD-L1 Detection, and Response to Transarterial Chemoembolization in Patients with Hepatocellular Carcinoma

“…Despite the above limitations, higher post-TACE sTIM-3 levels in complete responders may be attributed to the greater extent of tumor infiltration by TIM-3+ T lymphocytes in patients with better response to treatment. This finding has been previously described in cases of complete response to chemotherapy in other types of cancer [36]. Furthermore, a recent study in HCC patients has shown that yttrium-90 (Y90)-radioembolization (RE) induces an increase of PD-1+/TIM-3+ CD8+ T cells at 3 months post-treatment.…”

Immunogenomic profiles associated with response to neoadjuvant chemoradiotherapy in patients with rectal cancer

“…Neoantigen specific T cell priming is important for the efficacy of CRT, and immune checkpoint molecules may be therapeutic targets to achieve even better responses in rectal cancer. Mouse models have shown that the efficacy of radiotherapy largely depends on CD8+ T cells; the presence of pretreatment CD8+ TILs correlated with better response to radiotherapy or chemotherapy in breast, lung, head and neck, anal, and rectal cancer. However, most studies using pre‐CRT biopsies in rectal cancer did not analyse TIL and stromal lymphocytes separately.…”

“…Mouse models have shown that the efficacy of radiotherapy largely depends on CD8+ T cells; the presence of pretreatment CD8+ TILs correlated with better response to radiotherapy or chemotherapy in breast, lung, head and neck, anal, and rectal cancer. However, most studies using pre‐CRT biopsies in rectal cancer did not analyse TIL and stromal lymphocytes separately. One study that did analyse the two populations separately found that pre‐CRT CD8+ TIL density was associated with favourable TRG but not with improved RFS.…”

“…Preclinical and immunogenomic studies have demonstrated the important role of the host immune system in patient responses to radiotherapy. Tumour‐infiltrating lymphocyte (TIL) abundance in pretreatment biopsies may predict a better response to CRT. Several clinical trials are ongoing to test whether combining immune checkpoint inhibitors with CRT can improve rectal cancer regression (NCT 03127007, NCT03102047, NCT02948348).…”

Digital pathology-aided assessment of tumor-infiltrating T lymphocytes in advanced stage, HPV-negative head and neck tumors

“…This could mean that the pre-treatment composition of the tumor microenvironment is of less importance than the anti-tumor immune response induced by the (chemo)radiotherapy. However, this is not supported by multiple studies that do show an association between the pre-treatment presence of TILs and treatment outcome [14,55,56]. The correlation between biomarkers and OS, DFS, and LRC was assessed in a Cox proportional hazards regression.…”