• 제목, 요약, 키워드: tumor infiltrating lymphocytes

검색결과 21건 처리시간 0.046초

Associations Between Infiltrating Lymphocyte Subsets and Hepatocellular Carcinoma

  • Guo, Cun-Li;Yang, Hai-Chao;Yang, Xiu-Hua;Cheng, Wen;Dong, Tian-Xiu;Zhu, Wen-Jing;Xu, Zheng;Zhao, Liang
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5909-5913
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    • 2012
  • Aims: We aimed to analyze the phenotype of tumor-infiltrating lymphocytes (TILs) and non-tumor infiltrating lymphocytes (NILs) in HCC and non-tumor tissues, and evaluate relationships between changes in these cells and the prognosis of HCC. Methods: Lymphocytes were isolated from HCC and corresponding non-tumor tissues and tested by flow cytometry. For comparison, clinical parameters were analyzed. Results: Compared with the non-tumor tissue, tumor tissue had a lower intensity of NK, NKT andCD8+T cell infiltration. TILs had higher intensity of CD4+CD25+Foxp3+regulatory T cell (Treg cells) infiltration compared with that in NILs. The prevalence of Treg cells was associated with fewer CD8 + T lymphocytes in the HCC immune microenvironment. The frequencies of NK cells and CD8+T cells in TILs of HCC patients with metastasis less than 12 months were lower than those without metastasis. However, the frequency of Treg cells was higher than those without metastasis. Conclusion: These results suggest that the frequencies of CD8+T, NK and NKT cells as well as Treg cells in the tumor tissue of HCC are significantly associated with patient survival, and could be applied as predictive indicators for HCC prognosis.

Tumor Infiltrating Lymphocytes in Ovarian Cancer

  • Gasparri, Maria Luisa;Attar, Rukset;Palaia, Innocenza;Perniola, Giorgia;Marchetti, Claudia;Donato, Violante Di;Farooqi, Ammad Ahmad;Papadia, Andrea;Panici, Pierluigi Benedetti
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.9
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    • pp.3635-3638
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    • 2015
  • Several improvements in ovarian cancer treatment have been achieved in recent years, both in surgery and in combination chemotherapy with targeting. However, ovarian tumors remain the women's cancers with highest mortality rates. In this scenario, a pivotal role has been endorsed to the immunological environment and to the immunological mechanisms involved in ovarian cancer behavior. Recent evidence suggests a loss of the critical balance between immune-activating and immune-suppressing mechanisms when oncogenesis and cancer progression occur. Ovarian cancer generates a mechanism to escape the immune system by producing a highly suppressive environment. Immune-activated tumor infiltrating lymphocytes (TILs) in ovarian tumor tissue testify that the immune system is the trigger in this neoplasm. The TIL mileau has been demonstrated to be associated with better prognosis, more chemosensitivity, and more cases of optimal residual tumor achieved during primary cytoreduction. Nowadays, scientists are focusing attention on new immunologically effective tumor biomarkers in order to optimize selection of patients for recruitment in clinical trials and to identify relationships of these biomarkers with responses to immunotherapeutics. Assessing this point of view, TILs might be considered as a potent predictive immunotherapy biomarker.

Immunoregulatory Function of HLA-G in Gastric Cancer

  • Tuncel, Tolga;Karagoz, Bulent;Haholu, Aptullah;Ozgun, Alpaslan;Emirzeoglu, Levent;Bilgi, Oguz;Kandemir, Emin Gokhan
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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    • pp.7681-7684
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    • 2013
  • Background: Human leukocyte antigen (HLA)-G-positive gastric cancers are associated with poor survival, but links with tumor escape mechanisms remain to be determined. Materials and Methods: We used immunohistochemistry to investigate HLA-G expression, tumor infiltrating CD8+ T lymphocytes, and Treg cells in 52 gastric cancer patients. Results: There were 29 cancer-related deaths during the follow-up period. Kaplan-Meier analysis indicated that patients with HLA-G-positive (n=16) primary tumors had a significantly poorer prognosis than patients with HLA-G-negative tumors (n=36, p=0.008). The median survival time was 14 months and 47 months, respectively. Patients with high numbers of Tregs and low numbers of CD8+T lymphocytes in the primary tumor had a poorer prognosis than those with low numbers of Tregs and high numbers of CD8+T lymphocytes (p=0.034, p=0.043). Multivariate Cox proportional hazard regression analysis showed that HLA-G expression (hazard ratio: 2.662; 95% confidence interval: 1.242-5.723; p=0.012) and stage (hazard ratio: 2.012;95% confidence interval: 1.112-3.715; p=0.041) were independent unfavorable factors for patient survival. Conclusions: We found a significant positive correlation between HLA-G expression and the number of tumor infiltrating Tregs (p=0.01) and a negative correlation with the number of CD8+T lymphocytes (p=0.041). HLA-G may protect gastric cancer cells from cytolysis by inducing Foxp3+Treg lymphocytes and suppressing CD8+T lymphocytes.

Association between Chemotherapy-Response Assays and Subsets of Tumor-Infiltrating Lymphocytes in Gastric Cancer: A Pilot Study

  • Lee, Jee Youn;Son, Taeil;Cheong, Jae-Ho;Hyung, Woo Jin;Noh, Sung Hoon;Kim, Choong-Bai;Park, Chung-Gyu;Kim, Hyoung-Il
    • 대한위암학회지
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    • v.15 no.4
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    • pp.223-230
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    • 2015
  • Purpose: The purpose of this pilot study was to evaluate the association between adenosine triphosphate-based chemotherapy response assays (ATP-CRAs) and subsets of tumor infiltrating lymphocytes (TILs) in gastric cancer. Materials and Methods: In total, 15 gastric cancer tissue samples were obtained from gastrectomies performed between February 2007 and January 2011. Chemotherapy response assays were performed on tumor cells from these samples using 11 chemotherapeutic agents, including etoposide, doxorubicin, epirubicin, mitomycin, 5-fluorouracil (5-FU), oxaliplatin, irinotecan, docetaxel, paclitaxel, methotrexate, and cisplatin. TILs in the tissue samples were evaluated using antibodies specific for CD3, CD4, CD8, Foxp3, and Granzyme B. Results: The highest cancer cell death rates were induced by etoposide (44.8%), 5-FU (43.1%), and mitomycin (39.9%). Samples from 10 patients who were treated with 5-FU were divided into 5-FU-sensitive and -insensitive groups according to median cell death rate. No difference was observed in survival between the two groups (P=0.216). Only two patients were treated with a chemotherapeutic agent determined by an ATP-CRA and there was no significant difference in overall survival compared with that of patients treated with their physician's choice of chemotherapeutic agent (P=0.105). However, a high number of CD3 TILs was a favorable prognostic factor (P=0.008). Pearson's correlation analyses showed no association between cancer cell death rates in response to chemotherapeutic agents and subsets of TILs. Conclusions: Cancer cell death rates in response to specific chemotherapeutic agents were not significantly associated with the distribution of TIL subsets.

Association between p53 Expression and Amount of Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer

  • Lee, Miseon;Park, In Ah;Heo, Sun-Hee;Kim, Young-Ae;Gong, Gyungyub;Lee, Hee Jin
    • 대한병리학회지
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    • v.53 no.3
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    • pp.180-187
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    • 2019
  • Background: Most triple-negative breast cancers (TNBCs) have a high histologic grade, are associated with high endoplasmic stress, and possess a high frequency of TP53 mutations. TP53 missense mutations lead to the production of mutant p53 protein and usually show high levels of p53 protein expression. Tumor-infiltrating lymphocytes (TILs) accumulate as part of the anti-tumor immune response and have a strong prognostic and predictive significance in TNBC. We aimed to elucidate the association between p53 expression and the amount of TILs in TNBC. Methods: In 678 TNBC patients, we evaluated TIL levels and expression of endoplasmic stress molecules. Immunohistochemical examination of p53 protein expression was categorized into three groups: no, low, and high expression. Results: No, low, and high p53 expression was identified in 44.1% (n=299), 20.1% (n=136), and 35.8% (n=243) of patients, respectively. Patients with high p53 expression showed high histologic grade (p<.001), high TIL levels (p=.009), and high expression of endoplasmic reticulum stress-associated molecules (p-eIF2a, p=.013; XBP1, p=.007), compared to patients with low p53 expression. There was no significant difference in disease-free (p=.406) or overall survival rates (p=.444) among the three p53 expression groups. Conclusions: High p53 expression is associated with increased expression of endoplasmic reticulum stress molecules and TIL influx.

Expression of Epstein-Barr Virus Gene and Clonality of Infiltrated T Lymphocytes in Epstein-Barr Virus-associated Gastric Carcinoma

  • Lee, Jae-Myun;Kim, Ho-Guen;Noh, Sung-Hoon;Lee, Won-Young;Kim, Se-Jong;Park, Jeon-Han
    • IMMUNE NETWORK
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    • v.11 no.1
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    • pp.50-58
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    • 2011
  • Background: Epstein-Barr virus associated gastric lymphoepithelioma-like carcinoma (LELC) is characterized by the intensive infiltration of lymphoid cells, the presence of EBV, and the better prognosis over typical adenocarcinoma. Thus, it was assumable that viral latent proteins may be responsible for the recruitment of a certain T cell repertoire to EBV-associated gastric carcinoma. Methods: To examine above possibility, EBV gene expression in gastric carcinoma tissues and usage of TCR among the tumor infiltrating lymphocytes were analyzed. Results: EBV specific DNA and EBERs RNA were detected in 4 out of 30 patients. RT-PCR analysis revealed that all 4 of EBV-positive tumor tissues expressed EBNA1 mRNA and BARTs and LMP2a was detected only one sample out of 4. However, the EBNA2 and LMP-1 transcripts were not detected in these tissues. $CD8^+$ T cells were the predominant population of infiltrating lymphocytes in the EBV-positive gastric carcinoma. According to spectra type analysis of infiltrating T cells, 10 predominant bands were detected by TCR $V{\beta}$ CDR3 specific RT-PCR from 4 EBV-positive tumor tissues. Sequence analysis of these bands revealed oligoclonal expansion of T cells. Conclusion: These findings suggest that clonally expanded T cells in vivo might be a population of cytotoxic T cells reactive to EBV-associated gastric carcinoma.

Potential Utility of FDG PET-CT as a Non-invasive Tool for Monitoring Local Immune Responses

  • Lee, Seungho;Choi, Seohee;Kim, Sang Yong;Yun, Mi Jin;Kim, Hyoung-Il
    • 대한위암학회지
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    • v.17 no.4
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    • pp.384-393
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    • 2017
  • Purpose: The tumor microenvironment is known to be associated with the metabolic activity of cancer cells and local immune reactions. We hypothesized that glucose metabolism measured by 2-deoxy-2-($^{18}F$)fluoro-D-glucose ($^{18}F-FDG$) positron emission tomography (PET)-computed tomography (CT) ($^{18}F-FDG$ PET-CT) would be associated with local immune responses evaluated according to the presence of tumor infiltrating lymphocytes (TILs). Materials and Methods: We retrospectively reviewed 56 patients who underwent $^{18}F-FDG$ PET-CT prior to gastrectomy. In resected tumor specimens, TIL subsets, including cluster of differentiation (CD) 3, CD4, CD8, Forkhead box P3 (Foxp3), and granzyme B, were subjected to immunohistochemical analysis. The prognostic nutritional index (PNI) was calculated as: ($10{\times}serum$ albumin value)+($0.005{\times}peripheral$ lymphocyte counts). Additionally, the maximum standard uptake value ($SUV_{max}$) was calculated to evaluate the metabolic activity of cancer cells. Results: The $SUV_{max}$ was positively correlated with larger tumor size (R=0.293; P=0.029) and negatively correlated with PNI (R=-0.407; P=0.002). A higher $SUV_{max}$ showed a marginal association with higher CD3 (+) T lymphocyte counts (R=0.227; P=0.092) and a significant association with higher Foxp3 (+) T lymphocyte counts (R=0.431; P=0.009). No other clinicopathological characteristics were associated with $SUV_{max}$ or TILs. Survival analysis, however, indicated that neither $SUV_{max}$ nor Foxp3 held prognostic significance. Conclusions: FDG uptake on PET-CT could be associated with TILs, especially regulatory T cells, in gastric cancer. This finding may suggest that PET-CT could be of use as a non-invasive tool for monitoring the tumor microenvironment in patients with gastric cancer.

마렉병 바이러스 강독주의 실험 접종에 의해 유발된 닭 피부병변에 침윤한 림프구 표현형의 변화 (Phenotypical changes of lymphocyte subsets infiltrated in the skin lesions induced experimentally by very virulent strain of Marek's disease virus in chickens)

  • 조경오
    • 대한수의학회지
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    • v.41 no.3
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    • pp.373-380
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    • 2001
  • Marek's disease virus (MDV) can cause skin lesions including inflammatory to tumorous. The phenotypical changes of lymphocytes infiltrating in the skin lesions induced by MDV were not clear. Therefore, the skin biopsies taken at weekly intervals for 8 weeks from the same specific-pathogen free chickens inoculated with Md/5 MDV were examined to analysis the phenotypical changes of lymphocytes. Histologically skin lesions progressed from initial inflammatory to late tumorous. Sequentially CD4+ T lymphocytes increased gradually in number from initial skin lesions and were major composition cells in the tumor lesions. Regardless of inflammatory or tumor lesions, CD8+ T cells and ${\gamma}{\delta}$ T cells infiltrated particularly in the dermis and subcutaneous on which MDV was actively replicated in the feather follicle epithelium(FFE). In addition, IgG bearing B lymphocytes in considerable number infiltrated in the dermis and subcutaneous tissues. From these results, the development of MDV-induced skin lesions was inflammatory following tumorous. In addition, each CD8+, ${\gamma}{\delta}$ and CD4+ T cells and B cell might act to protect MDV replication in the FFE or tumor cells which turned on lytic cycle.

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T-Cell Immunoglobulin Mucin 3 Expression on Tumor Infiltrating Lymphocytes as a Positive Prognosticator in Triple-Negative Breast Cancer

  • Byun, Kyung Do;Hwang, Hyo Jun;Park, Ki Jae;Kim, Min Chan;Cho, Se Heon;Ju, Mi Ha;Lee, Jin Hwa;Jeong, Jin Sook
    • Journal of Breast Cancer
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    • v.21 no.4
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    • pp.406-414
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    • 2018
  • Purpose: T-cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) is an emerging immune response molecule related to T-cell anergy. There has been tremendous interest in breast cancer targeting immune checkpoint molecules, especially in the triple-negative breast cancer (TNBC). This study was designed to investigate TIM-3 expression on tumor infiltrating lymphocytes (TILs), its relationships with clinicopathological parameters and expression of programmed death receptor 1 (PD-1)/programmed death receptor ligand 1 (PD-L1), and its prognostic role. Methods: Immunohistochemistry on tissue microarray blocks produced from 109 samples of invasive ductal carcinoma type TNBC was performed with antibodies toward TIM-3, PD-1, PD-L1 and breast cancer-related molecular markers. Associations between their expression and clinicopathological parameters as well as survival analyses were performed. Results: TIM-3 was expressed in TILs from all 109 TNBCs, consisting of 17 cases (<5%), 31 cases (6%-25%), 48 cases (26%-50%), and 13 cases (>51%). High TIM-3 was significantly correlated with younger patients (p=0.0101), high TILs (p=0.0029), high tumor stage (p=0.0018), high PD-1 (p=0.0001) and high PD-L1 (p=0.0019), and tended to be associated with higher histologic grade, absence of extensive in situ components and microcalcification. High TIM-3 expression was significantly associated with a combinational immunophenotype group of high PD-L1 and high PD-1 (p<0.0001). High TIM-3 demonstrated a significantly better disease-free survival (DFS) (p<0.0001) and longer overall survival (OS) (p=0.0001), together with high TILs and high PD-1. In univariate survival analysis, high TIM-3 showed reduced relapse risk (p<0.0001) and longer OS (p=0.0003), together with high PD-1 expression. In multivariate analysis, high TIM-3 was statistically significant in predicting prognosis, showing better DFS (hazard ratio [HR], 0.0994; 95% confidence interval [CI], 0.0296-0.3337; p=0.0002) and longer OS (HR, 0.1109; 95% CI, 0.0314-0.3912; p=0.0006). Conclusion: In this study, we demonstrate that TIM-3 expression is an independent positive prognostic factor in TNBC, despite its association with poor clinical and pathologic features.

Expression of Myxovirus Resistance A (MxA) Is Associated with Tumor-Infiltrating Lymphocytes in Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancers

  • Lee, So Jeong;Hwang, Cheong-Soo;Kim, Young-Keum;Lee, Hyun Jung;Ahn, Sang-Jeong;Shin, Nari;Lee, Jung Hee;Shin, Dong Hoon;Choi, Kyung Un;Park, Do Youn;Lee, Chang Hun;Huh, Gi Young;Sol, Mi Young;Lee, Hee Jin;Gong, Gyungyub;Kim, Jee Yeon;Kim, Ahrong
    • Cancer Research and Treatment
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    • v.49 no.2
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    • pp.313-321
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    • 2017
  • Purpose The prognostic significance of tumor-infiltrating lymphocytes (TILs) has been determined in breast cancers. Interferons can affect T-cell activity through direct and indirect mechanisms. Myxovirus resistance A (MxA) is an excellent marker of interferon activity. Here,we evaluated TILs and MxA expression in human epidermal growth factor receptor 2 (HER2)-positive breast cancers. Materials and Methods Ninety cases of hormone receptor (HR)+/HER2+ tumors and 78 cases of HR-/HER2+ tumors were included. The TILs level was assessed using hematoxylin and eosin-stained full face sections, and MxA expression was evaluated by immunohistochemistry with a tissue microarray. Results MxA protein expression was significantly higher in tumors with high histologic grade (p=0.023) and high levels of TILs (p=0.002). High levels of TILs were correlated with high histological grade (p=0.001), negative lymphovascular invasion (p=0.007), negative lymph node metastasis (p=0.007), absence of HR expression (p < 0.001), abundant tertiary lymphoid structures (TLSs) around ductal carcinoma in situ (p=0.018), and abundant TLSs around the invasive component (p < 0.001). High levels of TILs were also associated with improved disease-free survival, particularly in HR-/HER2+ breast cancers. However, MxA was not a prognostic factor. Conclusion High expression of MxA in tumor cells was associated with high levels of TILs in HER2-positive breast cancers. Additionally, a high level of TILs was a prognostic factor for breast cancer, whereas the level of MxA expression had no prognostic value.