期刊
HISTOPATHOLOGY
卷 67, 期 5, 页码 730-739出版社
WILEY
DOI: 10.1111/his.12703
关键词
fibroblast-like cells; OSCC; prognosis; TLR-7; tumour-infiltrated lymphocytes
资金
- National Natural Science Foundation of China [81402238, 81072213, 81271698]
- Nanjing Medical Science and Research Project [YKK13145]
- Nanjing Medical Young engineer [QRX113311]
- National Key Disciplines Constructional Project Funding
- Jiangsu Provincial Clinical Medicine of Science and Technology project [BL2012017]
- Nanjing Municipal Key Medical Laboratory Constructional Project Funding
- Center of Nanjing Clinical Medicine of tumour project
AimsToll-like receptor (TLR)-7 agonists have been used in cancer immunotherapy, but tumour heterogeneity means that TLR-7 activity is variable in different components of the tumour microenvironment and the characteristics of TLR-7 in oral squamous cell carcinoma (OSCC) are unclear. Methods and resultsTwenty healthy oral tissues, 50 oral leukoplakia tissues and 166 retrospective primary OSCC samples were collected for immunohistochemical staining of TLR-7 and showed up-regulated expression during carcinogenesis. Moreover, patients with high expression of TLR-7 in tumour cells (TCs) had poor differentiation and prognosis. Interestingly, patients with high expression of TLR-7 in stroma fibroblast-like cells (FLCs) had low tumour stage, no lymph node metastasis (LNM) and better prognosis. Furthermore, Ki-67, CD3, CD4, CD8 and forkhead box protein 3 (FoxP3)(+) tumour-infiltrated lymphocytes were assessed and we found that TLR-7(high) TCs were infiltrated by fewer CD3(+)CD4(+) but more FoxP3(+) lymphocytes. Importantly, patients with TLR-7(low)TCs and TLR-7(high)FLCs had less FoxP3(+) lymphocyte infiltration and longer survival time than those with TLR-7(high)TCs/TLR-7(low)FLCs, although TLR-7 was not an independent prognostic factor for OSCC. ConclusionsThe low expression of TLR-7 in tumour and high expression of TLR-7 in stroma predict a good clinical outcome for OSCC patients, and stroma FLCs might be amenable to immunotherapy by a TLR-7 agonist.
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