Tumor Microenvironment in Mixed Neuroendocrine Non-Neuroendocrine Neoplasms: Interaction between Tumors and Immune Cells, and Potential Effects of Neuroendocrine Differentiation on the Tumor Microenvironment

Cancers

Tatsuya Hoshi¹  Yuko Itakura²  Ikuro Sato³  Kazuhiro Sakamoto⁴  Hiroyoshi Suzuki⁵  Takashi Sawai⁶  Hirofumi Watanabe⁷  Hironobu Sasano⁷  Fumiyoshi Fujishima⁷  Koh Miura⁸  Takashi Kamei⁹  Toshiaki Fukutomi⁹  Junichi Tsunokake⁹  Chiaki Sato⁹  Yohei Ozawa⁹  Yusuke Taniyama⁹  Hiroshi Okamoto⁹  Takuro Yamauchi⁹  Atsushi Kunimitsu⁹  Ryujiro Akaishi⁹ 

[1] Department of Internal Medicine, Kesennuma Citizen Hospital, Kesennuma 988-0181, Japan;Department of Pathology, Japanese Red Cross Ishinomaki Hospital, Ishinomaki 986-8522, Japan;Department of Pathology, Miyagi Cancer Center, Natori 981-1293, Japan;Department of Pathology, Osaki Citizen Hospital, Osaki 989-6183, Japan;Department of Pathology, Sendai Medical Center, Sendai 983-8520, Japan;Department of Pathology, Sendai Open Hospital, Sendai 983-0824, Japan;Department of Pathology, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan;Department of Surgery, Miyagi Cancer Center, Natori 981-1293, Japan;Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan;

关键词: mixed neuroendocrine non-neuroendocrine neoplasms;    tumor microenvironment;    tumor infiltrating lymphocyte;    neuroendocrine differentiation;    angiogenesis;    immune suppression;   

DOI  :  10.3390/cancers14092152

来源: DOAJ

【 摘 要 】

The tumor microenvironment is considered to play a pivotal role in various human malignancies. Neuroendocrine and non-neuroendocrine neoplasms are considered to have different tumor microenvironments. However, owing to differences in the systemic and/or local immune statuses, tumor microenvironments in different patients may be difficult to compare. Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs), although rare, could be useful for exploring the effects of neuroendocrine differentiation on the tumor microenvironment, because both neuroendocrine and non-neuroendocrine components are present in the same tumor. Here, we examined 33 cases of histologically confirmed MiNENs and evaluated the influence of neuroendocrine differentiation on the tumor microenvironment by comparing tumor-infiltrating lymphocytes, tumor-associated macrophages, and other relevant factors in the two components the same tumor. The immunoreactivity of those examined above was evaluated quantitatively. The values of vasohibin-1-positive density (p < 0.0001) and immunoreactivity (p < 0.0001) (representing the neoangiogenesis status) were significantly higher in neuroendocrine as compared to non-neuroendocrine areas of the same tumors. In addition, the Foxp3/CD8 (p = 0.0717) and the PD-1/CD8 ratios (p = 0.0176) (representing tumor immunity suppression) tend to increase in neuroendocrine carcinomas. Immunoreactivity of CD163, a marker of M2-like macrophages, was also higher in the neuroendocrine areas. Our findings indicate that neuroendocrine and non-neuroendocrine tumors differ from each other with respect to the characteristics of both tumor cells and the tumor microenvironment.

【 授权许可】

Unknown