CD8+ tumor-infiltrating lymphocytes within the primary tumor of patients with synchronous de novo metastatic colorectal carcinoma do not track with survival

Millen, Rosemary; Hendry, Shona; Narasimhan, Vignesh; Abbott, Rebecca; Croxford, Matthew; Gibbs, Peter; Tie, Jeanne; Wong, Hui-Li; Jones, Ian; Kosmider, Suzanne; Byrne, David; Zalcberg, John; Fox, Stephen; Desai, Jayesh; Visvanathan, Kumar; Ramsay, Robert G; Tran, Ben

Author(s): Millen, Rosemary; Hendry, Shona; Narasimhan, Vignesh; Abbott, Rebecca; Croxford, Matthew; Gibbs, Peter; Tie, Jeanne; Wong, Hui-Li; Jones, Ian; Kosmider, Suzanne; Byrne, David; Zalcberg, John; Fox, Stephen; Desai, Jayesh; Visvanathan, Kumar; Ramsay, Robert G; Tran, Ben;
Details: Publication Year 2020,Volume 9,Issue #7,Page e1155
Journal Title: Clinical & Translational Immunology
Publication Type: Journal Article
Abstract: Abstract Objectives Tumor-infiltrating lymphocytes (TIL), particularly CD8+ TILs in patients with colorectal cancer (CRC), are highly prognostic in the early-disease stages (I-II). In metastatic disease (stage IV; mCRC), their influence is less well defined. It has presumably failed to contain tumor cells to the primary site; however, is this evident? We explored the prognostic impact of TILs at the primary site in patients who presented de novo with mCRC. Methods Treatment-naïve patients (109) with mCRC were assessed for CD8+ TILs and PD-L1 expression. Microsatellite instability (MSI) was evaluated by IHC for PMS2 and MSH6 proteins and/or by PCR using the Bethesda panel. Results Microsatellite instability-high tumors had significantly more CD8+ TILs, with no significant survival advantage observed between MSI-H and microsatellite stable (MSS) tumors (12 vs 19 months, P = 0.304). TIL density for all cases had no impact on OS (low: 20 vs high: 13 months, P = 0.426), while PD-L1 of 1% or higher was associated with reduced mean survival (9.6 vs 18.9 months; P = 0.038). MSI-H tumors and associated immune cells had higher PD-L1 expression than in MSS cases. A positive correlation between PD-L1 on immune cells and CD8+ve TILs was found. A subset of MSS tumors had relatively high TILs approximating that of MSI-H tumors. Conclusion In contrast to early-stage CRC, the immune response in primary tumors of patients with de novo mCRC does not appear to influence survival. A subgroup of MSS tumors was identified with increased TILs/PD-L1 comparable to MSI-H tumors, traditionally not be considered for immune checkpoint blockade and perhaps should be.
Publisher: Wiley
Research Division(s): Personalised Oncology
PubMed ID: 32953115
Link To PubMed Central Version: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484874/
Publisher's Version: https://doi.org/10.1002/cti2.1155
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2020-08-05 11:11:25

Last Modified: 2020-09-23 10:15:47