Article Text
PDF
Abstract
Background Interactions between the immune system and the tumor are now recognized as key determinants of clinical outcome in colorectal cancer (CRC). Immune landscapes have been extensively studied within resected primary tumors and immune markers, such as T cells, have been found to be associated with CRC patients‘ survival. Little is known about the immune profile of cells in peripheral blood. We hypothesize that the functional status of T cells, characterized by their response to CRC tumor-associated antigens (TAAs), can be monitored in the peripheral blood of patients and that they have prognostic relevance in CRC.
Methods In vitro T cell responses to pools of overlapping peptides representing the TAAs MUC-1, hTERT, NY-ESO-1 and CEA were assessed by analyzing IFN-gamma and TNF-alpha production by CD8+ T cells using flow cytometry, in 5 stage II-III CRC patients just prior to surgical resection and 3 healthy age- and sex-matched controls.
Results T cells responding to MUC-1, hTERT, NY-ESO-1 and CEA were present in 3, 3, 1 and 5 CRC patients, respectively, whereas only one response to TAAs (MUC-1) was found in one healthy control (figure 1). When TAA responses were pooled together, 83.3% of responders were patients (n=5) and 100% of non-responders were healthy controls (n=2).
CRC TAA-specific CD8 T cell responses in CRC patieDot plot of one representative healthy control (#3) and one representative patient (#2) showing IFN-γ production by CD8 T cells in response to (A) MUC-1, hTERT, NY-ESO-1 and CEA stimulations or without any restimulation (negative control) and (B) positive controls (CEF and PMA/ionomycin). Percentages of IFN-gamma+ CD8 T cells are displayed in each plot. C Frequency of MUC-1-, hTERT-, NY-ESO-1-, CEA- and pooled TAA-specific CD8 T cell responses in patients (grey) and healthy controls (black). Fisher exact test, * p=0.0179; ns=not significant.
Conclusions The presence of circulating T cells responding to CEA in all 5 patients, but also to MUC-1 and hTERT in 3 patients suggests that these TAAs may be good targets for immunotherapy in CRC. Our findings also provide a rationale to investigate the prognostic value of CEA-, MUC-1- and hTERT-specific T cells in the peripheral blood of CRC patients and to consider vaccination with these antigens to boost or induce responses to control residual tumor post-surgery.
Ethics Approval This study was approved by Health Sciences North’s Research Ethics Board; approval number 18- 104.
This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.