Prognostic Relevance of Immunosuppressive CD155/TIGIT Signaling in Locally Advanced Rectal Cancer Patients With Neoadjuvant Chemoradiotherapy

Yuan-Yao Tsai; Tao-Wei Ke; Chi-Hsien Huang; Tsung-Wei Chen; Yu-Sen Lin; Te-Hong Chen; Hui-Yu Chen; William Tzu-Liang Chen; K S Clifford Chao; Kevin Chih-Yang Huang

doi:10.21873/anticanres.17420

Prognostic Relevance of Immunosuppressive CD155/TIGIT Signaling in Locally Advanced Rectal Cancer Patients With Neoadjuvant Chemoradiotherapy

Anticancer Res. 2025 Jan;45(1):323-333. doi: 10.21873/anticanres.17420.

Authors

Yuan-Yao Tsai^{1

2}, Tao-Wei Ke^{2

3}, Chi-Hsien Huang^{1

4}, Tsung-Wei Chen⁵, Yu-Sen Lin⁶, Te-Hong Chen^{7

8}, Hui-Yu Chen⁹, William Tzu-Liang Chen^{2

8

10}, K S Clifford Chao^{4

11

12}, Kevin Chih-Yang Huang^{13

14

15}

Affiliations

¹ Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan, R.O.C.
² Department of Colorectal Surgery, China Medical University Hospital, China Medical University, Taichung, Taiwan, R.O.C.
³ School of Chinese Medicine & Graduate Institute of Chinese Medicine, China Medical University, Taichung, Taiwan, R.O.C.
⁴ Department of Radiation Oncology, China Medical University Hospital, China Medical University, Taichung, Taiwan, R.O.C.
⁵ Department of Pathology, Asia University Hospital, Asia University, Taichung, Taiwan, R.O.C.
⁶ Department of Chest Surgery, China Medical University Hospital, Taichung, Taiwan, R.O.C.
⁷ Department of Surgery, China Medical University Hospital, Taichung, Taiwan, R.O.C.
⁸ School of Medicine, China Medical University, Taichung, Taiwan, R.O.C.
⁹ Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung, Taiwan, R.O.C.
¹⁰ Department of Colorectal Surgery, China Medical University HsinChu Hospital, China Medical University, HsinChu, Taiwan, R.O.C.
¹¹ Proton Therapy and Science Center, China Medical University Hospital, China Medical University, Taichung, Taiwan, R.O.C.
¹² Department of Radiotherapy, School of Medicine, China Medical University, Taichung, Taiwan, R.O.C.
¹³ Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung, Taiwan, R.O.C.; [email protected].
¹⁴ Translation Research Core, China Medical University Hospital, China Medical University, Taichung, Taiwan, R.O.C.
¹⁵ Cancer Biology and Precision Therapeutics Center, China Medical University, Taichung, Taiwan, R.O.C.

PMID: 39740825
DOI: 10.21873/anticanres.17420

Abstract

Background/aim: The CD155/TIGIT axis has recently emerged as a promising immunotherapeutic target in several malignancies. However, its prognostic relevance within the tumor microenvironment (TME) in patients with locally advanced rectal cancer (LARC) who have received neo-adjuvant chemoradiotherapy (neoCRT) remains unclarified.

Materials and methods: The levels of tumor CD155 and TIGIT⁺ T cells in pair-matched pre-neoCRT biopsies and post-neoCRT surgical tissues were evaluated in 110 LARC tissues using immunohistochemistry. The relationship between CD155, TIGIT⁺ T cells, and other clinicopathological parameters was analyzed.

Results: The level of tumor CD155 was significantly increased in the post-neoCRT surgical tissues, compared to pre-neoCRT biopsies (p=0.0491). Moreover, tumor CD155 expression correlated with increased risk of local recurrence (p=0.016) and the infiltration of CD3⁺ T cells in the post-neoCRT surgical tissues (p=0.026). Patients with high tumor CD155 were significantly associated with worsen 10-year disease-free survival (DFS), suggesting the prognostic value of tumor CD155 on DFS in LARC patients who received neoCRT treatment. However, no significant association was observed between TIGIT⁺ T cells and DFS in these patients.

Conclusion: Tumor CD155 may play a pivotal role in the response to neoCRT treatment through alternative immunological mechanisms and could become a novel immunotherapeutic target for LARC patients.

Keywords: CD155; DFS; Locally advanced rectal cancer; TIGIT.

MeSH terms

Adult
Aged
Chemoradiotherapy / methods
Disease-Free Survival
Female
Humans
Male
Middle Aged
Neoadjuvant Therapy* / methods
Neoplasm Recurrence, Local / pathology
Prognosis
Receptors, Immunologic* / metabolism
Receptors, Virus / metabolism
Rectal Neoplasms* / immunology
Rectal Neoplasms* / metabolism
Rectal Neoplasms* / pathology
Rectal Neoplasms* / therapy
Signal Transduction
Tumor Microenvironment*

Substances

poliovirus receptor
TIGIT protein, human
Receptors, Immunologic
Receptors, Virus