The spatial coexistence of TIGIT/CD155 defines poorer survival and resistance to adjuvant chemotherapy in pancreatic ductal adenocarcinoma

Ma, Heng; Chen, Xianlong; Mo, Shengwei; Mao, Xinxin; Chen, Jingci; Liu, Yilin; Lu, Zhaohui; Yu, Shuangni; Chen, Jie

doi:10.7150/thno.86547

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Nanotheranostics 2024; 8(4): 442-457. [Abstract] [Full text] [PDF]

Nanotheranostics 2024; 8(4): 427-441. [Abstract] [Full text] [PDF]

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Theranostics 2023; 13(13):4601-4614. doi:10.7150/thno.86547 This issue Cite

Research Paper

The spatial coexistence of TIGIT/CD155 defines poorer survival and resistance to adjuvant chemotherapy in pancreatic ductal adenocarcinoma

Heng Ma^*, Xianlong Chen^*, Shengwei Mo, Xinxin Mao, Jingci Chen, Yilin Liu, Zhaohui Lu, Shuangni Yu^#✉, Jie Chen^#✉

Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, 100730, China.
*These authors contributed equally to this work.
^#These authors jointly supervised this work.

Citation:

Ma H, Chen X, Mo S, Mao X, Chen J, Liu Y, Lu Z, Yu S, Chen J. The spatial coexistence of TIGIT/CD155 defines poorer survival and resistance to adjuvant chemotherapy in pancreatic ductal adenocarcinoma. Theranostics 2023; 13(13):4601-4614. doi:10.7150/thno.86547. https://www.thno.org/v13p4601.htm

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Abstract

Background: Targeting emerging T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT)/CD155 axis shows promise for restoring anti-tumor immunity, but its immune phenotypes and prognostic significance in a large cohort of pancreatic ductal adenocarcinoma (PDAC) are limited.

Methods: Three seven-color multispectral panels were rationally designed to investigate the protein expression, immune-microenvironmental feature, prognostic value, and the response to adjuvant chemotherapy of TIGIT/CD155 in 272 PDAC specimens using multiplex immunohistochemistry.

Results: We revealed low immunogenicity and high heterogeneity of the PDAC immune microenvironment featured by abundant CD3⁺ T cells and CD68⁺ macrophages and low infiltration of activated cytotoxic T lymphocytes. TIGIT and CD155 were highly expressed in PDAC tissues compared to paracancerous tissues. Tumor-infiltrating lymphocytes expressing TIGIT were correlated with high densities of CD45RO⁺ T cells; TIGTI⁺CD8⁺ T cells were associated with high infiltration of CD3⁺CD45RO⁺FOXP3⁺. CD155⁺CK⁺ were significantly related to high densities of CD3⁺ and CD3⁺CD8⁺CD45RO⁺ T cells. High positive rates for TIGIT in TCs, CD8⁺ T cells, and CD155 in macrophages were correlated with poor progression-free and disease-specific survival, respectively, and their clinical significance was correlated with PD-L1 status. Notably, spatial co-existence of TIGIT⁺CK⁺ or TIGIT⁺CD8⁺ and CD155⁺CD68⁺ indicated poor survival and resistance to adjuvant chemotherapy response in patients with PDAC.

Conclusion: Our findings suggest that targeting TIGIT/CD155 immunosuppressive axis may guide patient stratification and improve the clinical outcome of PDAC.

Keywords: Pancreatic ductal adenocarcinoma, TIGIT/CD155, PD-L1, adjuvant chemotherapy, multiplex immunohistochemistry

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APA

Ma, H., Chen, X., Mo, S., Mao, X., Chen, J., Liu, Y., Lu, Z., Yu, S., Chen, J. (2023). The spatial coexistence of TIGIT/CD155 defines poorer survival and resistance to adjuvant chemotherapy in pancreatic ductal adenocarcinoma. Theranostics, 13(13), 4601-4614. https://doi.org/10.7150/thno.86547.

ACS

Ma, H.; Chen, X.; Mo, S.; Mao, X.; Chen, J.; Liu, Y.; Lu, Z.; Yu, S.; Chen, J. The spatial coexistence of TIGIT/CD155 defines poorer survival and resistance to adjuvant chemotherapy in pancreatic ductal adenocarcinoma. Theranostics 2023, 13 (13), 4601-4614. DOI: 10.7150/thno.86547.

NLM

CSE

Ma H, Chen X, Mo S, Mao X, Chen J, Liu Y, Lu Z, Yu S, Chen J. 2023. The spatial coexistence of TIGIT/CD155 defines poorer survival and resistance to adjuvant chemotherapy in pancreatic ductal adenocarcinoma. Theranostics. 13(13):4601-4614.

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