An in vitro investigation into the cytotoxic impact of antigen-presenting dendritic cell-tumor infiltrating lymphocytes on ovarian cancer cells

Abstract Objective The objective of this study is to develop a novel therapeutic approach for the treatment of ovarian cancer while investigating the role of tumor-infiltrating lymphocytes (TILs) in the context of ovarian cancer therapy. The primary aim is to establish a technical procedure for the...

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Main Authors: Shengnan Yang, Junrong Wang, Zhenwu Du, Chunhua Sheng, Qianyu Liu, Xuewei Lao, Donghui Xu, Ying Pan
Format: Article
Language:English
Published: BMC 2024-11-01
Series:BMC Cancer
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Online Access:https://doi.org/10.1186/s12885-024-13131-7
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author Shengnan Yang
Junrong Wang
Zhenwu Du
Chunhua Sheng
Qianyu Liu
Xuewei Lao
Donghui Xu
Ying Pan
author_facet Shengnan Yang
Junrong Wang
Zhenwu Du
Chunhua Sheng
Qianyu Liu
Xuewei Lao
Donghui Xu
Ying Pan
author_sort Shengnan Yang
collection DOAJ
description Abstract Objective The objective of this study is to develop a novel therapeutic approach for the treatment of ovarian cancer while investigating the role of tumor-infiltrating lymphocytes (TILs) in the context of ovarian cancer therapy. The primary aim is to establish a technical procedure for the isolation of tumor cells, lymphocytes, and dendritic cells (DCs) derived from ovarian cancer tissues or ascites. Subsequently, the focus lies on the generation of dendritic cell-tumor infiltrating lymphocytes (DC-TILs) exhibiting specific cytotoxic capabilities aimed at targeted therapeutic interventions. The cytotoxic impact of DC-TIL interactions on tumor cells was investigated through in vitro experimentation. This research aims to provide fundamental experimental insights for the future clinical advancement of TIL therapy in ovarian cancer. Methods The experimental samples included fresh surgical specimens and ascites specimens procured from three patients (ranging in age from 32 to 75), sourced from the Department of Gynecology at the Third Bethune Hospital of Jilin University. TILs were extracted through in vitro isolation from solid tumor tissues, while primary tumor cells and DCs were obtained from ascites specimens. Tumor-specific antigens derived from patient tumor cells were utilized to stimulate the maturation of DCs. TILs were subsequently co-cultured with antigen-stimulated DC cells. Subsequently, TILs with specific killing effects were obtained, and the cytotoxic impact of DC-TILs on tumor cells was detected in vitro. Results (1) TILs were successfully obtained through expansion from the tumor tissue of a patient diagnosed with ovarian cancer. (2) DCs were successfully induced from ascites cells harvested from patients diagnosed with ovarian cancer. (3) TILs significantly enhanced the cytotoxicity of tumor cells following DC stimulation. Conclusion TILs have the capacity to augment the cytotoxicity directed towards tumor cells following DC stimulation.
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spelling doaj-art-7338328e9a284a6c88719f10d6fa96402025-08-20T02:50:01ZengBMCBMC Cancer1471-24072024-11-0124111110.1186/s12885-024-13131-7An in vitro investigation into the cytotoxic impact of antigen-presenting dendritic cell-tumor infiltrating lymphocytes on ovarian cancer cellsShengnan Yang0Junrong Wang1Zhenwu Du2Chunhua Sheng3Qianyu Liu4Xuewei Lao5Donghui Xu6Ying Pan7Department of Gynecologic, The Third Bethune Hospital of Jilin UniversityDepartment of Gynecologic, The Third Bethune Hospital of Jilin UniversityDepartment of Orthopedics, The Second Norman Bethune Hospital of Jilin UniversityDepartment of Oncology, Changchun Tumor HospitalDepartment of Gynecologic, The Third Bethune Hospital of Jilin UniversityDepartment of Gynecologic, The Third Bethune Hospital of Jilin UniversityDepartment of Gynecologic, Shuangyang District Traditional Chinese Medicine HospitalDepartment of Gynecologic, The Third Bethune Hospital of Jilin UniversityAbstract Objective The objective of this study is to develop a novel therapeutic approach for the treatment of ovarian cancer while investigating the role of tumor-infiltrating lymphocytes (TILs) in the context of ovarian cancer therapy. The primary aim is to establish a technical procedure for the isolation of tumor cells, lymphocytes, and dendritic cells (DCs) derived from ovarian cancer tissues or ascites. Subsequently, the focus lies on the generation of dendritic cell-tumor infiltrating lymphocytes (DC-TILs) exhibiting specific cytotoxic capabilities aimed at targeted therapeutic interventions. The cytotoxic impact of DC-TIL interactions on tumor cells was investigated through in vitro experimentation. This research aims to provide fundamental experimental insights for the future clinical advancement of TIL therapy in ovarian cancer. Methods The experimental samples included fresh surgical specimens and ascites specimens procured from three patients (ranging in age from 32 to 75), sourced from the Department of Gynecology at the Third Bethune Hospital of Jilin University. TILs were extracted through in vitro isolation from solid tumor tissues, while primary tumor cells and DCs were obtained from ascites specimens. Tumor-specific antigens derived from patient tumor cells were utilized to stimulate the maturation of DCs. TILs were subsequently co-cultured with antigen-stimulated DC cells. Subsequently, TILs with specific killing effects were obtained, and the cytotoxic impact of DC-TILs on tumor cells was detected in vitro. Results (1) TILs were successfully obtained through expansion from the tumor tissue of a patient diagnosed with ovarian cancer. (2) DCs were successfully induced from ascites cells harvested from patients diagnosed with ovarian cancer. (3) TILs significantly enhanced the cytotoxicity of tumor cells following DC stimulation. Conclusion TILs have the capacity to augment the cytotoxicity directed towards tumor cells following DC stimulation.https://doi.org/10.1186/s12885-024-13131-7AscitesDendritic cellsImmunotherapyOvarian cancerTumor infiltrating lymphocytes
spellingShingle Shengnan Yang
Junrong Wang
Zhenwu Du
Chunhua Sheng
Qianyu Liu
Xuewei Lao
Donghui Xu
Ying Pan
An in vitro investigation into the cytotoxic impact of antigen-presenting dendritic cell-tumor infiltrating lymphocytes on ovarian cancer cells
BMC Cancer
Ascites
Dendritic cells
Immunotherapy
Ovarian cancer
Tumor infiltrating lymphocytes
title An in vitro investigation into the cytotoxic impact of antigen-presenting dendritic cell-tumor infiltrating lymphocytes on ovarian cancer cells
title_full An in vitro investigation into the cytotoxic impact of antigen-presenting dendritic cell-tumor infiltrating lymphocytes on ovarian cancer cells
title_fullStr An in vitro investigation into the cytotoxic impact of antigen-presenting dendritic cell-tumor infiltrating lymphocytes on ovarian cancer cells
title_full_unstemmed An in vitro investigation into the cytotoxic impact of antigen-presenting dendritic cell-tumor infiltrating lymphocytes on ovarian cancer cells
title_short An in vitro investigation into the cytotoxic impact of antigen-presenting dendritic cell-tumor infiltrating lymphocytes on ovarian cancer cells
title_sort in vitro investigation into the cytotoxic impact of antigen presenting dendritic cell tumor infiltrating lymphocytes on ovarian cancer cells
topic Ascites
Dendritic cells
Immunotherapy
Ovarian cancer
Tumor infiltrating lymphocytes
url https://doi.org/10.1186/s12885-024-13131-7
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