Journal
CANCER IMMUNOLOGY IMMUNOTHERAPY
Volume 70, Issue 2, Pages 509-518Publisher
SPRINGER
DOI: 10.1007/s00262-020-02705-6
Keywords
Rectal cancer; Chemoradiotherapy; T-cell receptor repertoire; Tumor-infiltrating lymphocyte
Categories
Funding
- JSPS KAKENHI [18K08664, 18K08635, 20K09022]
- Foundation for Promotion of Cancer Research in Japan
- Grants-in-Aid for Scientific Research [18K08664, 18K08635, 20K09022] Funding Source: KAKEN
Ask authors/readers for more resources
This study found that patients with increased pre-treatment CD8(+)TIL density and high TCR diversity index had better responses to chemoradiotherapy in rectal cancer, serving as predictive factors for good response to CRT.
Emerging evidence suggests that an increased density of pre-treatment CD8(+)tumor-infiltrating lymphocytes (TILs) is associated with good response to chemoradiotherapy (CRT) in patients with locally advanced rectal cancer. However, the significance of T-cell complexity in the clinical setting remains unknown. High-throughput T-cell receptor (TCR) beta sequencing was applied to quantify the TCR repertoire of pre-treatment biopsies from 67 patients with advanced rectal cancer receiving preoperative CRT. Diversity index was used to represent the complexity of the TCR repertoire in a tumor. Pre-treatment CD8(+)TIL densities were assessed by immunohistochemistry. Changes in TCR repertoire before and after CRT were also analysed in 23 patients. Diversity indices were significantly higher for good responders than for non-responders (P = 0.031). The multivariate analysis revealed that both CD8(+)TIL density and TCR diversity index were independently associated with good response to CRT (P < 0.001 andP = 0.049, respectively). Patients who were high for both CD8(+)TIL density and TCR diversity (double-high) had markedly better responses to CRT than double-low patients (84.2% vs 16.7%,P < 0.0001). Larger changes in TCR repertoires before and after CRT were correlated with better recurrence-free survival (P = 0.027). The complexity and dynamic change in the TCR repertoire might serve as a useful indicator of response to CRT in combination with CD8(+)TIL density in patients with rectal cancer.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available