1.Study on infiltrated lymphocytes in lung cancer
Journal of Medical Research 2003;26(6):12-16
73 cases of lung cancer were studied at the Institute of Tuberculosis and Lung diseases. The infiltration of lymphocytes in the tissue of primary lung cancer in operation was investigated. HE staining method was used, 47 cases stained by immunochemicals with antiCD3, CD20, CD8 antibodies. Lymphoid infiltration was observed in 64% of cancer tissues, among them 42,5% of cases there is a infiltration of high level lymphoid infiltration was identified in chorial tissues and intertialis tissues. The form of cyste was localized only in chorial tissue.
neoplasms
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Lung Neoplasms
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Lymphocytes
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Lymphocytes, Tumor-Infiltrating
2.The immunological characteristics of tumor infiltrating lymphocytes and tumor draining lymph node lymphocytes in advanced stomach cancer.
Jae Yong LEE ; Jung Soon JANG ; Young Iee PARK ; Noe Kyeong KIM ; Chee Young CHOE ; Woo Ho KIM ; Chul Woo KIM ; Young Il KIM ; Dae Seog HEO ; Woo Hyun CHANG
Journal of the Korean Cancer Association 1992;24(5):656-665
No abstract available.
Lymph Nodes*
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Lymphocytes*
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Lymphocytes, Tumor-Infiltrating*
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Stomach Neoplasms*
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Stomach*
3.Function of tumor infiltrating lymphocytes in solid tumors - a review.
Suhang BAI ; Xiaoyue YANG ; Nan ZHANG ; Fuhan ZHANG ; Zongyi SHEN ; Na YANG ; Wensai ZHANG ; Changyuan YU ; Zhao YANG
Chinese Journal of Biotechnology 2019;35(12):2308-2325
Tumor is one of the major diseases threatening human health in the 21st century. Surgical resection, radiotherapy, chemotherapy and targeted therapy are the main clinical treatments for solid tumors. However, these methods are unable to eradicate tumor cells completely, and easily lead to the recurrence and progression of tumor. Tumor immunotherapy is a novel treatment that uses human immune system to control and kill tumor by enhancing or restoring anti-tumor immunity. Tumor immunotherapy has shown to produce long-lasting responses in large numbers of patients, and thereby adoptive immunotherapy and immune checkpoint inhibitors could induce remarkable antigen-specific immune responses. Tumor infiltrating lymphocytes (TILs) are highly heterogeneous lymphocytes existing in tumor tissues and play a crucial role in host antigen-specific tumor immune response. Recent studies show that TILs are closely related to the prognosis of patients during the processes of tumorigenesis and treatment. Adoptive immunotherapy mediated by TILs has displayed favorable curative effect in many solid tumors. This paper reviews the recent progress of TILs in solid tumors.
Humans
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Immunotherapy
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Lymphocytes
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Lymphocytes, Tumor-Infiltrating
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Neoplasms
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Prognosis
4.Changes of Tumor-infiltrating Lymphocytes in Breast Cancer after Neoadjuvant Chemotherapy.
Hyun Joo SHIN ; Hee Joon KANG ; Jin Wook CHOI ; Soo Kee MIN ; Eun Young KO ; Lee Su KIM
Journal of the Korean Surgical Society 2005;69(5):367-373
PURPOSE: Neoadjuvant chemotherapy for breast cancer creates new possibilities for the analysis of biological factors in the tumor and/or host, which may play a role in the response to treatment. In this study, whether changes in tumor infiltrating lymphocytes take place after neoadjuvant chemotherapy, and if these correlate with the response to treatment in breast cancer were analyzed. METHODS: Neoadjuvant chemotherapy (Adriamycin: 50 mg/m2 +docetaxel: 75 mg/m2, q3wks, 3 treatments) was followed by definitive surgical management. Histological sections from the pre-treatment core-needle biopsy and post-treatment surgical specimens of 17 patients were analyzed for the extent of lymphocytes infiltration. Infiltrated lymphocytes have been recognized as tumor-infiltrating lymphocytes (TILs; lymphocytes present within tumor cell nests). The modified Black's scoring system was used for grading the extent of lymphocytes infiltration, with immunohistochemical (IHC) staining used to characterize the TILs. RESULTS: Pre-treatment lymphocytic infiltrates within the tumor were minimal in the majority of patients, and showed no relationship with the response. A marked increase of TILs after chemotherapeutic treatment was noted in patients according to the following response; complete response: 4/4 (100%), partial response: 2/6 (33.3%), stable disease: 0/7 (0%) (P=0.004). Histological sections stained with IHC staining revealed the increased TILs were CD8 positive cytotoxic T-lymphocytes. CONCLUSION: These results suggest that the development of TILs after treatment correlate with the response to neoadjuvant chemotherapy. Despite the limitation of this preliminary study, the extent of TILs change might be used as a predictor for the therapeutic efficacy of neoadjuvant chemotherapy in breast cancer.
Biological Factors
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Biopsy
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Breast Neoplasms*
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Breast*
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Drug Therapy*
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Humans
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Lymphocytes
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Lymphocytes, Tumor-Infiltrating*
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T-Lymphocytes, Cytotoxic
5.Roles of Tumor Infiltrating Lymphocytes in Hematologic Malignancies-Review.
Ming LIANG ; Hui ZHANG ; Fu-Xiong CHEN
Journal of Experimental Hematology 2016;24(4):1241-1247
Hematologic malignancies are the most common childhood malignancy and the main cause of death in pediatric cancer patients. Systemic diagnosis and risk-based treatment in these 30 years have achived a great improvement in pediatric cancer therapy, for example, the event-free 5-years survival rate of childhood acute lymphoblastic leukemia was over 80%. Unfortunately, 20%-25% patients relapsed after-therapy, therefore, the novel therapeutic strategies that can improve survival are urgently required. T lymphocytes are the most potent effective anti-tumor cells. Tumor infiltrating lymphocytes comprise many heterotypic lymphocytes, which mainly are T cells for the adoptive cellular immunotherapy. The success of hematopoietic stem cell transplantation in leukemia therapy indicated that the functional recovery of immune cells plays a significant role in the treatment of hematologic malignancies. The cancer immunotherapy become a new strategy for malignancies, while the role of immunotherapy in hematologic malignancies still remained rarely understood. Herein, the recent research progress about the roles of tumor infiltrating lymphocyte and its potential application for hematologic malignancies are systemically reviewed.
Hematopoietic Stem Cell Transplantation
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Humans
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Immunotherapy, Adoptive
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Lymphocytes, Tumor-Infiltrating
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T-Lymphocytes
6.Establishment of culture system for selective amplification of CD8+ T cells in vitro and analysis of its functional and molecular phenotypes from tumor-infiltrating lymphocytes in malignant pleural/ascites.
Jiameng LIU ; Chaoming MAO ; Fei YE ; Xiao YUAN
Chinese Journal of Cellular and Molecular Immunology 2023;39(4):311-317
Objective To explore the culture method of mass amplification for tumor-infiltrating lymphocytes (TILs) from malignant pleural/ascites in vitro, and identify the function and molecular phenotype of these amplified cells. Methods The pleural/ascites fluid was extracted under aseptic conditions, and lymphocytes were isolated by density gradient centrifugation. Then TILs were amplified by the program based on combined IFN-γ, OKT3 and IL-2, and the cell morphology and growth rate were recorded. The molecular phenotypes of the amplified lymphocytes were analyzed by Flow cytometry, and the killing ability against tumor cells was detected by CCK-8 assay. Results In this culture program, TILs remained in good condition until the 26th day, and the proliferation rate began to decrease on the 30th day. The proportions of CD4-CD8+ and CD8+CD56+ T cells gradually increased as cell culture time extended while the proportions of CD4+CD25+ T cells decreased gradually. Unlike the proportions prior to amplification, the proportions of SLAMF7, CD45RO, PD-1 and granzyme B positive cells in T lymphocyte subpopulation were significantly increased, meanwhile, the expression of exhausted T-cell marker CD57 was also gradually increased. The cytotoxicity of amplified CD8+ T cells from TILs was significantly stronger than that from PBMC, and the cytotoxicity reached the peak at the effect-target ratio of 10:1 and was significantly different among tumor cell types. Conclusion A culture program for TILs amplification from cancerous thoracic/ascites is established. The method is simple and efficient. The effector cells are mainly CD8+ T lymphocytes with active phenotype.
Humans
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CD8-Positive T-Lymphocytes
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Lymphocytes, Tumor-Infiltrating
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Ascites/metabolism*
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Phenotype
7.Progress of Tumor Infiltrating Lymphocytes in Immunotherapy of Triple Negative Breast Cancer.
Jia-Lin ZHAO ; Xue-Jing WANG ; Xi CAO ; Qiang SUN
Acta Academiae Medicinae Sinicae 2021;43(3):475-480
Breast cancer has become the most common cancer for women in China.Lack of effective therapeutic targets,triple negative breast cancer(TNBC)has poorer prognosis compared with other subtypes of breast cancer.Tumor infiltrating lymphocytes(TILs)are a group of heterogeneous lymphocytes around the tumor,which are believed as immunoreactive products of host immune response to tumor antigens.At present,there have been reports on the predictive effect of TILs on the prognosis of breast cancer,and the available studies focus mainly on TNBC.This article briefly reviews the recent progress of tumor infiltrating lymphocytes in immunotherapy of TNBC.
Biomarkers, Tumor
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China
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Female
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Humans
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Immunotherapy
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Lymphocytes, Tumor-Infiltrating
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Prognosis
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Triple Negative Breast Neoplasms/therapy*
8.Artificial intelligence-based analysis of tumor-infiltrating lymphocyte spatial distribution for colorectal cancer prognosis.
Ming CAI ; Ke ZHAO ; Lin WU ; Yanqi HUANG ; Minning ZHAO ; Qingru HU ; Qicong CHEN ; Su YAO ; Zhenhui LI ; Xinjuan FAN ; Zaiyi LIU
Chinese Medical Journal 2024;137(4):421-430
BACKGROUND:
Artificial intelligence (AI) technology represented by deep learning has made remarkable achievements in digital pathology, enhancing the accuracy and reliability of diagnosis and prognosis evaluation. The spatial distribution of CD3 + and CD8 + T cells within the tumor microenvironment has been demonstrated to have a significant impact on the prognosis of colorectal cancer (CRC). This study aimed to investigate CD3 CT (CD3 + T cells density in the core of the tumor [CT]) prognostic ability in patients with CRC by using AI technology.
METHODS:
The study involved the enrollment of 492 patients from two distinct medical centers, with 358 patients assigned to the training cohort and an additional 134 patients allocated to the validation cohort. To facilitate tissue segmentation and T-cells quantification in whole-slide images (WSIs), a fully automated workflow based on deep learning was devised. Upon the completion of tissue segmentation and subsequent cell segmentation, a comprehensive analysis was conducted.
RESULTS:
The evaluation of various positive T cell densities revealed comparable discriminatory ability between CD3 CT and CD3-CD8 (the combination of CD3 + and CD8 + T cells density within the CT and invasive margin) in predicting mortality (C-index in training cohort: 0.65 vs. 0.64; validation cohort: 0.69 vs. 0.69). The CD3 CT was confirmed as an independent prognostic factor, with high CD3 CT density associated with increased overall survival (OS) in the training cohort (hazard ratio [HR] = 0.22, 95% confidence interval [CI]: 0.12-0.38, P <0.001) and validation cohort (HR = 0.21, 95% CI: 0.05-0.92, P = 0.037).
CONCLUSIONS
We quantify the spatial distribution of CD3 + and CD8 + T cells within tissue regions in WSIs using AI technology. The CD3 CT confirmed as a stage-independent predictor for OS in CRC patients. Moreover, CD3 CT shows promise in simplifying the CD3-CD8 system and facilitating its practical application in clinical settings.
Humans
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Lymphocytes, Tumor-Infiltrating
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Colorectal Neoplasms
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Artificial Intelligence
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Reproducibility of Results
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Prognosis
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CD8-Positive T-Lymphocytes
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Tumor Microenvironment
9.The Clinical Significance of Tumor-Infiltrating Lymphocytes and Microscopic Satellites in Acral Melanoma in a Korean Population.
Seok Jong LEE ; Hyun Jung LIM ; Yoon Hyuk CHOI ; Yong Hyun CHANG ; Weon Ju LEE ; Do Won KIM ; Ghil Suk YOON
Annals of Dermatology 2013;25(1):61-66
BACKGROUND: There are various histological prognostic parameters of cutaneous malignant melanoma, including tumor thickness and ulceration. Tumor-infiltrating lymphocytes (TIL) are among these parameters and can be further classified into three categories: 'absent', 'non-brisk' and 'brisk'. Brisk TIL usually indicates better clinical prognosis. Microscopic satellite (Ms) is defined as a nest of tumor cells that is greater than 0.05 mm in diameter and definitely separated from the main tumor. Even though the incidence of Ms varies according to Breslow thickness, the presence of Ms generally indicates poor prognosis. OBJECTIVE: Clinical significance of both TIL and Ms has been extensively studied in western populations but much less so in Asian countries, including Korea, where acral melanoma is the most common subtype. METHODS: We reviewed 90 patients with acral melanoma diagnosed at Kyungpook National University Hospital in Korea. Tissue specimens were examined using hematoxylin-eosin and HMB45 immunohistochemical staining. They were also evaluated by the presence and categorization of TIL (absent, non-brisk and brisk) and the presence of Ms. We further evaluated their impact on survival events (recurrence, distant metastasis and death). RESULTS: The number of survival events by TIL type was 22 in the absent category (22/64, 34.4%), 3 in the non-brisk category (3/25, 12.0%) and 0 in the brisk category. For Ms, survival events were present in 7 patients in Ms-present group (7/11, 63.6%) and 21 patients in Ms-absent group (21/79, 26.6%). CONCLUSION: We suggest the possibility of TIL and Ms as prognostic indicators for acral melanoma in Korean population.
Asian Continental Ancestry Group
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Humans
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Incidence
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Korea
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Lymphocytes, Tumor-Infiltrating
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Melanoma
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Neoplasm Metastasis
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Prognosis
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Ulcer
10.A Study of Fas / Fas - Expression and Apoptosis according to the Progression of Gastric Adenocarclnoma.
Sung Chul LIM ; Jeong Hwan CHANG
Journal of the Korean Cancer Association 1999;31(6):1101-1111
PURPOSE: The purpose of this study was to determine whether Fas-L expression is associated with increased apoptotic induction of tumor-infiltrating lymphocytes (TIL) in human gastric carcinomas. MATERIALS AND METHODS: The author analysed 38 cases of early gastric carcinoma (EGC) and 61 cases of advanced gastric carcinoma (AGC) who received gastric resection, in whom the number of diffuse type was 38 cases and the number of intestinal type was 61 cases. The author used immunohistochemical staining for Fas, Fas-L and CD45, and TUNEL in situ apoptosis detection kit. TIL were detected by CD45 and apoptosis of TIL were detected by CD45 expression and TUNEL positivity on serial histologic sections. RESULTS: Fas-L was localized to neoplastic cells in 61% (23/38) of EGC group and 66% (40/61) of AGC group. The extent of Fas-L expression was variable, with both Fas-L positive and negative neoplastic region occuring within tumors. TIL adjacent to Fas-L expressing tumor region were decreased in number and TIL adjacent to FasL-negative tumor region were increased in number; apoptotic induction of TIL showed just the opposite pattern (p<0.05). Fas expression was found essentially homogeneously throughout the tumor mass independent of tumor stage. Fas expression showed 64% (39/61) of intestinal type and 68% (26/38) of diffuse type. Labeling indices for tumoral apoptosis in EGC and AGC were 6.72% and 7.13%, respectively and this difference was statistically insignificant. Co-expression of Fas-L and Fas, which occurred over large areas of the tumors, did not result in an enhanced rate of tumor cell apoptosis. In addition, factors such as tumor stage and other prognostic factors were not concerned in Fas and Fas-L expression, number of TIL and apoptotic induction. CONCLUSION: These findings suggest Fas-mediated apoptotic depletion of TIL in response to Fas-L expression by stomach cancers, and provide the evidence to support the Fas counterattack as a mechanism of immune escape in gastric cancer. In addition, gastric carcinoma cells of the intestinal and diffuse type did not differ in their expression of the apoptotic receptor Fas.
Apoptosis*
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Humans
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In Situ Nick-End Labeling
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Lymphocytes, Tumor-Infiltrating
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Stomach Neoplasms
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United Nations