Tumour-infiltrating regulatory T cell density before neoadjuvant chemoradiotherapy for rectal cancer does not predict treatment response

Abstract

Neoadjuvant (preoperative) chemoradiotherapy (CRT) decreases the risk of rectal cancer recurrence and reduces tumour volume prior to surgery. However, response to CRT varies considerably between individuals and factors associated with response are poorly understood. Foxp3+ regulatory T cells (Tregs) inhibit anti-tumour immunity and may limit any response to chemotherapy and radiotherapy. We have previously reported that a low density of Tregs in the tumour stroma following neoadjuvant CRT for rectal cancer is associated with improved tumour regression. Here we have examined the association between Treg density in pre-treatment diagnostic biopsy specimens and treatment response, in this same patient cohort. We aimed to determine whether pre-treatment tumour-infiltrating Treg density predicts subsequent response to neoadjuvant CRT. Foxp3+, CD8+ and CD3+ cell densities in biopsy samples from 106 patients were assessed by standard immunohistochemistry (IHC) and evaluated for their association with tumour regression grade and survival. We found no association between the density of any T cell subset pre-treatment and clinical outcome, indicating that tumour-infiltrating Treg density does not predict response to neoadjuvant CRT in rectal cancer. Taken together with the findings of the previous study, these data suggest that in the context of neoadjuvant CRT for rectal cancer, the impact of chemotherapy and/or radiotherapy on anti-tumour immunity may be more important than the state of the pre-existing local immune response.

Tumor-infiltrating Treg, MDSC, and IDO expression associated with outcomes of neoadjuvant chemotherapy of breast cancer

“…In a recent study that focused on Tregs, McCoy et al found that tumor-infiltrating Tregs prior to NCT for rectal tumors were not correlated with response. 34 However, in their previous study in 2016, a low density of Foxp3 C Tregs within the tumor stroma after NCT was shown to be strongly associated with pCR. 22 Baras et al reported that the ratio of CD8 C T cells to Tregs in situ was significantly related to a response to NCT in patients with muscle invasive urothelial cancer of the bladder.…”

Potential immune priming of the tumor microenvironment with FOLFOX chemotherapy in locally advanced rectal cancer

“…23 No strong relationship between pretreatment Tregs and treatment response has been observed, suggesting that the type of immune response generated by RT is more important. 24 The patient with a complete clinical response had the largest increase in MHC-I expression. High MHC-I expression reflects increased antigen presentation and is considered a measure of Figure 2.…”

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

“…The association between the density of Foxp3 + TILs and the response to neoadjuvant therapy also remains unclear, with conflicting findings reported. Indeed, some reports have found that a low density of Foxp3 + TILs after neoadjuvant CRT for rectal cancer was associated with a complete response, whereas others have found that the density of Foxp3 + TILs before and after neoadjuvant therapy for rectal cancer was not associated with the response to treatment …”