TY - JOUR
T1 - Immunological status of peripheral blood is associated with prognosis in patients with bone and soft-tissue sarcoma
AU - Kim, Youngji
AU - Kobayashi, Eisuke
AU - Suehara, Yoshiyuki
AU - Ito, Ayumu
AU - Kubota, Daisuke
AU - Tanzawa, Yoshikazu
AU - Endo, Makoto
AU - Nakatani, Fumihiko
AU - Nakatsura, Tetsuya
AU - Kawai, Akira
AU - Kaneko, Kazuo
AU - Kitano, Shigehisa
N1 - Funding Information:
Shigehisa Kitano reports personal fees from Astra Zeneca, Chugai Pharmaceutical Co., Ltd., Pfizer, Inc., Sanofi S.A., Nippon Kayaku Co., Ltd., Meiji Seika Kaisha, Ltd., Taiho Pharmaceutical Co., Ltd., Novartis International AG, Daiichi‑Sankyo Co., Ltd., personal fees from Merck Sharp and Dohme Corp., Kyowa Kirin Co., Ltd., Celgene Corporation, Sumitomo Dainippon Pharma Co., Ltd., Astellas Pharma, Inc., Ono Pharmaceutical Co., Ltd., Bristol‑Myers Squibb Company, AYUMI Pharmaceutical Corporation, Rakuten Medical, Inc., and Pharmaceuticals and Medical Devices Agency. In addition, grants and personal fees from Boehringer Ingelheim, Eisai Co., Ltd., and Regeneron Pharmaceuticals, Inc., and grants from Gilead Sciences, Inc., Japan Agency for Medical Research and Development, and Japan Society for the Promotion of Science, outside the submitted work.
Funding Information:
This study was supported by the Japan Society for the Promotion of science (JSPS), Grant‑in Aid for Scientific Research (B) (grant no. 15H04964), JSPS, Grant‑in Aid for Scientific Research (C) (grant no. 17K07208), JSPS, Grant‑in Aid for Young Scientists B) (grant no. 16K20076), JSPS, Grant‑in Aid for Young Scientists (grant no. 18K16634) and the Uehara Memorial Foundation and The Nakatomi Foundation.
Publisher Copyright:
© 2021 Spandidos Publications. All rights reserved.
PY - 2021/3
Y1 - 2021/3
N2 - Immune‑checkpoint inhibitors have shown promising antitumor effects against certain types of cancer. However, specific immune‑checkpoint inhibitors for patients with sarcoma have yet to be identified, whereas the immu‑ nological status of peripheral blood in patients with bone sarcoma and soft‑tissue sarcoma (STS) remains unknown. In addition, it is unclear whether the immunological status from the peripheral blood could be used as a prognostic indicator. Therefore, the present study aimed to clarify the immunological status of peripheral blood samples derived from patients with bone sarcoma and STS. Immune moni‑ toring was performed using the peripheral blood samples of 61 patients with no metastasis of high‑grade sarcoma. A total of 25 patients with metastatic sarcoma were used for comparison. A total of 41 immune cell subsets were analyzed using multicolor‑flow cytometry. The patients that did not have metastasis demonstrated higher quantities of monocytic myeloid‑derived suppressor cells (M‑MDSCs) and T cell immunoglobulin and mucin domain‑3 (Tim‑3)+ CD8+ T cells, which were significantly associated with poor disease‑free survival (DFS) time, while higher quantities of NKG2D+ CD8+ T cells were significantly associated with improved DFS time. Multivariate Cox regression analysis demonstrated that the number of Tim‑3+ CD8+ T cells was associated with lower DFS time. A significant association was also found between the number of M‑MDSCs and progression‑free survival (PFS) time in patients with metastasis. The results suggested the occurrence of immune surveillance, which indicated that the host immune reaction against cancer existed in patients with bone sarcoma and STS. Notably, a high number of M‑MDSCs was associated with both DFS and PFS time, suggesting a strong prognostic value. The data suggested that the immune status of peripheral blood was associated with the prognosis in patients with sarcoma, as previously reported in patients with other cancer types. In summary, the results may assist with the development of novel strategies for sarcoma treatment, based on the use of biomarkers or immunotherapy.
AB - Immune‑checkpoint inhibitors have shown promising antitumor effects against certain types of cancer. However, specific immune‑checkpoint inhibitors for patients with sarcoma have yet to be identified, whereas the immu‑ nological status of peripheral blood in patients with bone sarcoma and soft‑tissue sarcoma (STS) remains unknown. In addition, it is unclear whether the immunological status from the peripheral blood could be used as a prognostic indicator. Therefore, the present study aimed to clarify the immunological status of peripheral blood samples derived from patients with bone sarcoma and STS. Immune moni‑ toring was performed using the peripheral blood samples of 61 patients with no metastasis of high‑grade sarcoma. A total of 25 patients with metastatic sarcoma were used for comparison. A total of 41 immune cell subsets were analyzed using multicolor‑flow cytometry. The patients that did not have metastasis demonstrated higher quantities of monocytic myeloid‑derived suppressor cells (M‑MDSCs) and T cell immunoglobulin and mucin domain‑3 (Tim‑3)+ CD8+ T cells, which were significantly associated with poor disease‑free survival (DFS) time, while higher quantities of NKG2D+ CD8+ T cells were significantly associated with improved DFS time. Multivariate Cox regression analysis demonstrated that the number of Tim‑3+ CD8+ T cells was associated with lower DFS time. A significant association was also found between the number of M‑MDSCs and progression‑free survival (PFS) time in patients with metastasis. The results suggested the occurrence of immune surveillance, which indicated that the host immune reaction against cancer existed in patients with bone sarcoma and STS. Notably, a high number of M‑MDSCs was associated with both DFS and PFS time, suggesting a strong prognostic value. The data suggested that the immune status of peripheral blood was associated with the prognosis in patients with sarcoma, as previously reported in patients with other cancer types. In summary, the results may assist with the development of novel strategies for sarcoma treatment, based on the use of biomarkers or immunotherapy.
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U2 - 10.3892/ol.2021.12473
DO - 10.3892/ol.2021.12473
M3 - Article
AN - SCOPUS:85099805449
SN - 1792-1074
VL - 21
JO - Oncology Letters
JF - Oncology Letters
IS - 3
M1 - 212
ER -
