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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.
Affiliation
  • Ma H; Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, 100730, China.
  • Chen X; Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, 100730, China.
  • Mo S; Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, 100730, China.
  • Mao X; Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, 100730, China.
  • Chen J; Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, 100730, China.
  • Liu Y; Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, 100730, China.
  • Lu Z; Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, 100730, China.
  • Yu S; Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, 100730, China.
  • Chen J; Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, 100730, China.
Theranostics ; 13(13): 4601-4614, 2023.
Article in En | MEDLINE | ID: mdl-37649613
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pancreatic Neoplasms / Carcinoma, Pancreatic Ductal Type of study: Prognostic_studies Limits: Humans Language: En Journal: Theranostics Year: 2023 Document type: Article Affiliation country: China

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pancreatic Neoplasms / Carcinoma, Pancreatic Ductal Type of study: Prognostic_studies Limits: Humans Language: En Journal: Theranostics Year: 2023 Document type: Article Affiliation country: China