Inflammation in gastric adenocarcinoma of the cardia: how do EBV infection, Her2 amplification and cancer progression influence tumor-infiltrating lymphocytes?

2011 ◽  
Vol 458 (4) ◽  
pp. 403-411 ◽  
Author(s):  
Matthias Haas ◽  
Maike Büttner ◽  
Tilman T. Rau ◽  
Rainer Fietkau ◽  
Gerhard G. Grabenbauer ◽  
...  
Keyword(s):  
Gastric Adenocarcinoma ◽  
Cancer Progression ◽  
Tumor Infiltrating Lymphocytes ◽  
Her2 Amplification ◽  
Ebv Infection ◽  
Infiltrating Lymphocytes

Association of the ratio of CD8+ and CD163+ lymphocytes with clinical outcome in hepatocellular carcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15613-e15613
Author(s):  
Huan Chen ◽  
Haibei Xin ◽  
Lihong Wu ◽  
Yanhui Chen ◽  
Hongli Luo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Outcome ◽  
Cancer Progression ◽  
Immune Cell ◽  
Association Studies ◽  
Progression Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Disease Recurrence ◽  
Macrophage Density ◽  
Infiltrating Lymphocytes

e15613 Background: Within the tumor microenvironment (TME), infiltrating lymphocytes and myeloid cells including tumor-associated macrophages (TAMs) and tumor-associated neutrophils (TANs) are key players involved in liver cancer progression. The purpose of the study was to explorer whether distinct infiltrated immune cell features differentially affect clinical outcome in hepatocellular carcinoma (HCC). Methods: We obtained respectable stage II HCC specimens, along with adjacent para-tumor tissues from 221 patients who underwent surgical resection at Eastern Hepatobiliary Surgery Hospital, (in Shanghai, China) from 2015 through April 2018. CD8+, CD163+ and CD66B+ tumor-infiltrating lymphocytes (TILs) in the cancer area (CA) and stroma area (SA), as well paratumor stroma area, were analyzed by multiple immunohistochemistry. Results: Hierarchical clustering analysis of immune cell densities revealed that all HCC samples can be classified into three distinct groups. The three immune oncology types (IO-types) were characterized by a strong CD8 T cell density in CA and SA region (IO-1), an intermediate state of CD8 and CD163+ (IO-2), and a strong CD163+ macrophage density in IO-3. Remarkably increasing risks of mortality and recurrence, as well as elevated AST, ALP, GGT and AFP levels, were identified in IO-3 group, when compared with IO-1 group. We then identified that percentages of CA-CD8+ TILs in the tumor sample and SA-CD163+ macrophages in the para-tumor region showed opposite distribution pattern among the three IO types, suggesting a predictive role for CD8/TAM ratio in HCC cohort. Therefore, we next classified all HCC samples into two subgroups, according to the levels of tumor-CA-CD8/paratumor-SA-CD163 ratio. Expectedly, higher rate of CD8/CD163 represented significantly improved overall survival (OS) and progression free survival (PFS), verses lower rate of CD8/CD163. Further association studies suggested that the two subgroups correlated with HBV DNA, tumor size, and microvascular invasion (MVI). Of note, a prognostic signature combining portal vein tumor thrombus (PVTT) and CD8/CD163 ratio discriminated HCC patients into four subtypes with increasing risk of mortality and recurrence. Conclusions: The current results indicated that the CD8/CD163 is a novel, independent prognostic factor for a lower rate of disease recurrence and favorable OS in patients with resectable HCC.

Decreased density of CD3+ tumor-infiltrating lymphocytes during gastric cancer progression

2014 ◽  
Vol 29 (7) ◽  
pp. 1435-1441 ◽  
Author(s):  
Takaaki Arigami ◽  
Yoshikazu Uenosono ◽  
Sumiya Ishigami ◽  
Daisuke Matsushita ◽  
Tetsushi Hirahara ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Tumor Infiltrating Lymphocytes ◽  
Infiltrating Lymphocytes ◽  
Gastric Cancer Progression

scholarly journals The B-Side of Cancer Immunity: The Underrated Tune

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 449 ◽  
Author(s):  
Anne Largeot ◽  
Giulia Pagano ◽  
Susanne Gonder ◽  
Etienne Moussay ◽  
Jerome Paggetti
Keyword(s):  
B Cells ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Tumor Infiltrating Lymphocytes ◽  
Response To Therapy ◽  
Cancer Immunity ◽  
Infiltrating Lymphocytes ◽  
Precise Role ◽  
New Strategies

Tumor-infiltrating lymphocytes are known to be critical in controlling tumor progression. While the role of T lymphocytes has been extensively studied, the function of B cells in this context is still ill-defined. In this review, we propose to explore the role of B cells in tumor immunity. First of all we define their dual role in promoting and inhibiting cancer progression depending on their phenotype. To continue, we describe the influence of different tumor microenvironment factors such as hypoxia on B cells functions and differentiation. Finally, the role of B cells in response to therapy and as potential target is examined. In accordance with the importance of B cells in immuno-oncology, we conclude that more studies are required to throw light on the precise role of B cells in the tumor microenvironment in order to have a better understanding of their functions, and to design new strategies that efficiently target these cells by immunotherapy.

HER2-amplification level and tumor-infiltrating lymphocytes in breast cancer patients treated with neoadjuvant trastuzumab.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 596-596
Author(s):  
Cristina Masini ◽  
Giancarlo Bisagni ◽  
Moira Ragazzi ◽  
Alessandra Bisagni ◽  
Katiuscia Dallaglio ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Tumor Infiltrating Lymphocytes ◽  
Breast Cancer Patients ◽  
Her2 Amplification ◽  
Infiltrating Lymphocytes

scholarly journals The identification of tumor-infiltrating lymphocytes in patients with stomach cancer

2021 ◽  
Vol 23 (2) ◽  
pp. 307-312
Author(s):  
Gulnoz G. Khakimova ◽  
Yana A. Bozhchenko ◽  
Tatyana N. Zabotina ◽  
Alexey A. Tryakin
Keyword(s):  
Overall Survival ◽  
Stomach Cancer ◽  
Gastric Adenocarcinoma ◽  
Predictive Factors ◽  
Tnm Classification ◽  
Survival Rates ◽  
Tumor Infiltrating Lymphocytes ◽  
Spatial Location ◽  
Tumor Infiltration ◽  
Infiltrating Lymphocytes

Background. Stomach cancer (SC) is the 6th most common neoplasm among cancers (1 033 701 cases; 5.7%) and the 3rd most deadly cancer worldwide for men and women (782 685 deaths, 8.2%). SC therapy is a complex treatment associated with surgery, adjuvant chemotherapy, targeted therapy and immunotherapy with checkpoint inhibitors, nowadays. Despite the fact that the SC understanding has significantly increased within recent years, the prognosis still remains poor. In addition, very often the patients with the same stage of SC according to the international TNM classification of malignant tumors have different overall survival. Therefore, in order to improve survival rates, is necessary to understand the mechanisms of disease progression and to find new effective predictive factors. Besides many SC predictive factors, such as clinical and morphological characteristics (Lauren histologic type of tumor, degree of differentiation), biomarkers, deficient mismatch repair (dMMR), we have also revealed the positive correlation between the degree of tumor infiltration of tumor-infiltrating lymphocytes (TILs), especially with the spatial location of cell types (intratumoral or stromal cells), and the survival indicators of the patients with malignant neoplasms, recently. Moreover, TILs are the most significant predictive factors in patient survival rates than the TNM classification. At the same time, TILs predictive role in SC is still not clearly defined. Thus, the understanding of the degree of tumor infiltration of TILs depending on the spatial location would allow to determine the predictive significance, as well as to determine the direction of the immune reactions generating in patients with SC at the tissue level, depending on the risk and probability of progression. Aim. To study the predictive significance of intratumoral and stromal CD4+TILs, CD8+TILs and CD4+/CD8+TILs in patients with gastric adenocarcinoma. Materials and methods. From 2017 to 2018, 45 previously untreated patients with gastric adenocarcinoma (25 patients with stages IIII, 20 patients with stage IV) received surgical/combined treatment or independent chemotherapy, respectively, at the Blokhin National Medical Research Center of Oncology. The histological material was carried out before the treatment. Intratumoral (iTILs) and stromal (sTILs) values of CD4+TILs, CD8+TILs, CD4/CD8+TILs and the predictive significance in respect of overall survival and progression-free survival (PFS) were studied. Results. During the observation period (16.46.2 months) CD4+/CD8+iTILs were factors of poor prognosis concerning PFS in patients of the first group (p=0.035; odds ratio OR 3.264, 95% confidence interval CI). We also identified the statistically significant decrease in CD4+iTILs, CD8+iTILs, CD4+/CD8+iTILs and the absence of CD4+sTILs, CD8+sTILs, CD4+/CD8+sTILs in patients with metastatic SC (р=0.0003; р=0.000004; р=0.00001). Conclusion. The results show the positive predictive significance of CD4+sTILs, CD8+sTILs, CD4+/CD8+sTILs. At the same time, the increase of CD4+/CD8+iTILs reduces the PFS in patients with early and locally advanced SC.

scholarly journals Functional delineation of tissue-resident CD8+ T cell heterogeneity during infection and cancer

2020 ◽  
Author(s):  
J. Justin Milner ◽  
Clara Toma ◽  
Zhaoren He ◽  
Nadia S. Kurd ◽  
Quynh P. Nguyen ◽  
...  
Keyword(s):  
T Cells ◽  
Cancer Progression ◽  
Bacterial Infections ◽  
Regulatory Gene ◽  
Tumor Infiltrating Lymphocytes ◽  
Lymphoid Tissues ◽  
Acute Infections ◽  
Protection Against Infection ◽  
Infiltrating Lymphocytes ◽  
Discrete Populations

AbstractUnremitting defense against diverse pathogens and malignancies requires a dynamic and durable immune response. Tissue-resident memory CD8+ T cells (Trm) afford robust protection against infection and cancer progression through continuous surveillance of non-lymphoid tissues. Here, we provide insight into how Trm confer potent and persistent immunity through partitioning of distinct cellular subsets differing in longevity, effector function, and multipotency. Antigen-specific CD8+ T cells localized to the epithelium of the small intestine are primarily comprised of a shorter-lived effector population most prominent early following both acute viral and bacterial infections, and a longer-lived Id3hi Trm population that subsequently accumulates at later memory timepoints. We define regulatory gene-programs driving these distinct Trm states, and further clarify roles for Blimp1, T-bet, Id2, and Id3 in supporting and maintaining intestinal Trm heterogeneity during infection. Further, through single-cell RNAseq analysis we demonstrate that tumor-infiltrating lymphocytes broadly differentiate into discrete populations of short-lived and long-lived Trm-like subsets, which share qualities with terminally-exhausted and progenitor-exhausted cells, respectively. As the clinical relevance of Trm continues to widen from acute infections to settings of chronic inflammation and malignancy, clarification of the spectrum of phenotypic and functional states exhibited by CD8+ T cells that reside in non-lymphoid tissues will provide a framework for understanding their regulation and identity in diverse pathophysiological contexts.

scholarly journals Plasminogen Activating Inhibitor-1 Might Predict the Efficacy of Anti-PD1 Antibody in Advanced Melanoma Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Kentaro Ohuchi ◽  
Yumi Kambayashi ◽  
Takanori Hidaka ◽  
Taku Fujimura
Keyword(s):  
Cancer Progression ◽  
Tumor Infiltrating Lymphocytes ◽  
Serum Levels ◽  
Melanoma Cells ◽  
Immunomodulatory Effects ◽  
Baseline Serum ◽  
Melanoma Patients ◽  
Infiltrating Lymphocytes ◽  
Pai 1

Plasminogen activating inhibitor-1 (PAI-1) plays crucial roles in the development of various cancers, including melanomas. Indeed, various pro-tumorigenic functions of PAI-1 in cancer progression and metastasis have been widely reported. Among them, PAI-1 is also reported as a key regulator of PD-L1 expression on melanoma cells through endocytosis, leading to abrogating the efficacy of anti-PD1 antibodies (Abs). These findings suggested that PAI-1 expression might predict the efficacy of anti-PD1 Abs. In this report, the expression and production of PAI-1 in melanoma patients were evaluated, and the immunomodulatory effects of PAI-1 on tumor-associated macrophages were investigated in vitro. Immunohistochemical staining of PAI-1 showed that PAI-1 expression on melanoma cells was significantly decreased in responders compared to non-responders. Moreover, baseline serum levels of PAI-1 were significantly decreased in responders compared to non-responders. Notably, PAI-1 decreased the production of various chemokines from monocyte-derived M2 macrophages in vitro, suggesting that PAI-1 might decrease tumor-infiltrating lymphocytes to hamper the anti-tumor effects of anti-PD1 Abs. These results suggest that baseline serum levels of PAI-1 may be useful as a biomarker for identifying patients with advanced cutaneous melanoma most likely to benefit from anti-melanoma immunotherapy.

scholarly journals B Cells as an Immune-Regulatory Signature in Ovarian Cancer

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 894 ◽  
Author(s):  
Gupta ◽  
Chen ◽  
Chaluvally-Raghavan ◽  
Pradeep
Keyword(s):  
Ovarian Cancer ◽  
B Cells ◽  
Cancer Progression ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Tumor Infiltrating Lymphocytes ◽  
Therapeutic Interventions ◽  
Disease Stage ◽  
Gynecological Malignancy ◽  
Infiltrating Lymphocytes

Increasing evidence suggests that the immune system plays a dynamic role in the progression of ovarian cancer, the deadliest gynecological malignancy worldwide. Accumulation of tumor-infiltrating lymphocytes has been associated with increased survival in ovarian cancer patients, and diverse interactions among immune cells in the tumor microenvironment determine tumor progression. While the regulatory functions of T cells among tumor-infiltrating lymphocytes are well defined and also involve therapeutic interventions, the role of B cells in ovarian cancer progression is still limited to their impact on survival. Recent studies have identified both pro- and anti-tumor responses of B cells in solid tumors, as different subsets of B cells play diverse roles in progression. Thus, in-depth characterization of B cell subtypes in each disease stage is crucial for understanding the importance and therapeutic potential of these cells in ovarian cancer. In this review, we summarize current knowledge about B cells in ovarian cancer and discuss emerging therapeutic interventions that could harness B cells to combat this deadly disease.

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