The Clinicopathological Characteristics, Prognosis and Immune Microenvironment Mapping in MSI-H/MMR-D Endometrial Carcinomas

Abstract Endometrial cancer had a relatively high prevalence of MMR deficiency. MMR-D/MSI-H endometrial cancer patients are suggested to be potential beneficiaries of PD-1/PD-L1 inhibitor therapy. Here, we explored the prognostic value of MSI subtype in endometrial cancer and its correlation with immune environment. Based on expression and clinical data of 78 POLE, 123 MSI and 299 Other EC samples from the TCGA-UCEC project, we found that the MSI tumors were identified more often in early stage, had a lower age, better patient survival, enriched CD8+ T cells, and regulatory T cells and less M2 macrophages and activated dendritic cells than the Other subgroup, and shared a relatively similar expression profile with POLE subgroup by differential analysis. In addition, we established the immune landscape of an MMR-D endometrial cancer tissue using unbiased single-cell RNA-seq analysis of 4518 cells. By immunohistochemistry analysis, we found that the MMR-D tumors showed a higher trend of CD20+ B cells infiltration. Our study might expand our understanding of the role of immune subsets in MSI endometrial carcinomas and provide guidance of immunotherapy for endometrial cancer.

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Preoperative and intraoperative assesment of myometrial invasion and histological grade in endometrial cancer: Role of MRI and frozen section

10.1055/s-0039-1685336 ◽

2016 ◽

Author(s):

Rohit Raghunath Ranade

Keyword(s):

Endometrial Cancer ◽

Tumor Size ◽

Early Stage ◽

Frozen Section ◽

Myometrial Invasion ◽

Tumor Grade ◽

Endometrial Biopsy ◽

Intraoperative Frozen Section ◽

Cervical Involvement

Introduction: The role of systematic lymphadenectomy in clinically early stage endometrial cancer is controversial. A number of factors can predict lymph node metastasis including myometrial invasion, tumor grade in endometrial cancers. The purpose of the present study is to evaluate the accuracy of preoperative MRI and intraoperative frozen section in determining the depth of myometrial invasion, cervical involvement, tumor size and lymph nodal status. We also studied the accuracy of preoperative endometrial biopsy and intraoperative frozen section in determining the grade of the tumor. Materials and Methods: Medical records of 235 consecutive cases of clinically early stage endometrial cancer were reviewed retrospectively. A record of depth of myometrial invasion, tumor size, cervical involvement and presence of enlarged lymph nodes was made on a preoperative MRI. Similarly depth of myometrial invasion, tumor size, cervical involvement and grade of the tumor were recorded on an intraoperative frozen section. The grade of the tumor was also recorded on a preoperative endometrial biopsy. Standard statistical calculations were used. Results: The sensitivity and specificity of MRI for myometrial invasion for the first 160 cases were 81.3 and 75%, respectively while that for frozen section were 80 and 96.2%, respectively. For tumor grade the sensitivity and specificity of preoperative endometrial biopsy were 60 and 95.6%, respectively while that of frozen section were 53.8 and 97.6%, respectively. For cervical involvement the sensitivity of MRI and frozen section was 62.5 and 98.4%, respectively. Updated results of the entire cohort of 235 cases will be presented at the conference if selected. Conclusion: Although the sensitivity of both frozen section and MRI for predicting deep myometrial invasion was similar (80 vs 81.3%) but the specificity (96.2 vs 75%) and negative predictive value (92.7 vs 88.2%) of frozen section were superior to MRI. Both preoperative biopsy and intraoperative frozen section had low sensitivity (60 vs 53.8%) for detecting a high grade lesion.

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Controversies in the Treatment of Early Stage Endometrial Carcinoma

Obstetrics and Gynecology International ◽

10.1155/2012/578490 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 16

Author(s):

Joshua Z. Press ◽

Walter H. Gotlieb

Keyword(s):

Endometrial Cancer ◽

Adjuvant Chemotherapy ◽

Early Stage ◽

Sentinel Lymph Node Mapping ◽

Optimal Management ◽

Lymph Node Mapping ◽

Randomized Controlled ◽

Extent Of Surgery ◽

Early Stage Endometrial Cancer

Despite the publication of numerous studies, including some multicentered randomized controlled trials, there continues to be vigorous debate regarding the optimal management of early stage endometrial cancer, including the extent of surgery and the role of adjuvant chemotherapy and radiation. Resolving these questions has become increasingly important in view of the increase of endometrial cancer, related to the aging population and the alarming incidence of obesity. Furthermore, there are more surgical challenges encountered when operating on elderly patients or on patients with increased BMI and the associated comorbidities, such as diabetes, hypertension, heart disease, and pulmonary dysfunction. This paper will focus on the advantages of minimally invasive surgery, the value of lymphadenectomy including sentinel lymph node mapping, and some of the current controversies surrounding adjuvant chemotherapy and radiation.

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Protective Role of Naturally Occurring Interleukin-17A-Producing γδ T Cells in the Lung at the Early Stage of Systemic Candidiasis in Mice

Infection and Immunity ◽

10.1128/iai.05799-11 ◽

2011 ◽

Vol 79 (11) ◽

pp. 4503-4510 ◽

Cited By ~ 55

Author(s):

Takashi Dejima ◽

Kensuke Shibata ◽

Hisakata Yamada ◽

Hiromitsu Hara ◽

Yoichiro Iwakura ◽

...

Keyword(s):

T Cells ◽

Early Stage ◽

Γδ T Cells ◽

Protective Role ◽

Dependent Manner ◽

Peripheral Tissues ◽

Content Type ◽

Naturally Occurring ◽

Interleukin 17A

ABSTRACTInterleukin-17A (IL-17A)-producing γδ T cells differentiate in the fetal thymus and reside in the peripheral tissues, such as the lungs of naïve adult mice. We show here that naturally occurring γδ T cells play a protective role in the lung at a very early stage after systemic infection withCandida albicans.Selective depletion of neutrophils byin vivoadministration of anti-Ly6G monoclonal antibody (MAb) impaired fungal clearance more prominently in the lung than in the kidney 24 h after intravenous infection withC. albicans.Rapid and transient production of IL-23 was detected in the lung at 12 h, preceding IL-17A production and the influx of neutrophils, which reached a peak at 24 h after infection. IL-17A knockout (KO) mice showed reduced infiltration of neutrophils concurrently with impaired fungal clearance in the lung after infection. The major source of IL-17A was the γδ T cell population in the lung, and Cδ KO mice showed little IL-17A production and reduced neutrophil infiltration after infection. Early IL-23 production in a TLR2/MyD88-dependent manner and IL-23-triggered tyrosine kinase 2 (Tyk2) signaling were essential for IL-17A production by γδ T cells. Thus, our study demonstrated a novel role of naturally occurring IL-17A-producing γδ T cells in the first line of host defense againstC. albicansinfection.

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The role of L1CAM in early-stage endometrial cancer recurrence

Gynecologic Oncology ◽

10.1016/j.ygyno.2018.04.136 ◽

2018 ◽

Vol 149 ◽

pp. 61

Author(s):

C.M. Dahl ◽

S. Bedell ◽

L. Uppendahl ◽

T. Pulver ◽

R. Hellweg ◽

...

Keyword(s):

Endometrial Cancer ◽

Early Stage ◽

Cancer Recurrence ◽

Early Stage Endometrial Cancer

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Tamoxifen and Endometrial Cancer

Cancer Control ◽

10.1177/107327489600300202 ◽

1996 ◽

Vol 3 (2) ◽

pp. 107-112 ◽

Cited By ~ 1

Author(s):

Richard R. Barakat

Keyword(s):

Breast Cancer ◽

Endometrial Cancer ◽

Large Scale ◽

Early Stage ◽

Tamoxifen Treatment ◽

Breast Cancer Patients ◽

Menopausal Women ◽

Overall Survival Benefit ◽

Post Menopausal

Tamoxifen is commonly used in the management of patients with breast cancer. Clinical trials of tamoxifen involving over 75,000 patients demonstrate an improved recurrence-free and overall survival benefit in both pre- and post-menopausal women. Large-scale trials also are evaluating the role of tamoxifen as a chemopreventive agent in women considered to be at high risk for developing breast cancer based on family history. Endometrial cancer is an uncommon complication of tamoxifen therapy. Since the majority of these cancers will be detected at an early stage when they are highly curable, however, the overall benefit of tamoxifen treatment in breast cancer patients outweighs this risk. All women receiving tamoxifen who have a uterus should undergo regular gynecologic examinations.

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DUAL REGULATORY ROLE OF THE THYMUS IN THE MATURATION OF IMMUNE RESPONSE IN THE RABBIT

Journal of Experimental Medicine ◽

10.1084/jem.139.1.108 ◽

1974 ◽

Vol 139 (1) ◽

pp. 108-127 ◽

Cited By ~ 25

Author(s):

Masaru Taniguchi ◽

Tomio Tada

Keyword(s):

Immune Response ◽

T Cells ◽

Antibody Response ◽

Early Stage ◽

Early Adulthood ◽

Antibody Affinity ◽

Specific Antibody Response ◽

Different Doses

Rabbits thymectomized in early adulthood produced more antihapten antibody than sham-thymectomized controls after hyperimmunization with 2,4-dinitrophenyl bovine gamma globulin (DNP-BGG). The average associated constant of anti-DNP antibody produced by thymectomized animals was more than 10 times higher than that of the controls. Similar effects were obtained by extensive treatment of rabbits with antithymocyte serum (ATS) before and during the immunization with DNP-BGG. The results indicated that relative diminution of thymus-derived lymphocytes (T cells) resulted in a stimulation of antibody-forming cells with a higher affinity. On the other hand, preimmunization of rabbits with different doses of BGG caused either enhancement or suppression of the hapten-specific antibody response, depending on the priming dose of BGG. The suppressed antibody response was always associated with a marked decrease in the antibody affinity. If rabbits were partially tolerized with a large dose of soluble BGG, some of the animals produced little antibody against hapten (DNP) coupled to this carrier, and the affinity of produced antibody was low. However, other rabbits tolerized with BGG produced large amounts of anti-DNP antibody upon hyperimmunization with DNP-BGG, whose affinity was only slightly lower than that of the control. These results can be harmonized if it is assumed that the thymus plays an important role in the maturation of the immune response. It is postulated that T cells, in numbers ordinarily available, would first assist in the proliferation of antihapten antibody-forming cell precursors already selected by antigen, thus accounting for the rapid increase of antibody affinity in the early stage of immunization. However, after a larger number of carrier-specific T cells are made in response to continued immunization, these would suppress antibody-forming cells. The suppression would be greater for cells with higher affinity for antigen, resulting in a decrease in antibody affinity. This postulate explains preferential stimulation and suppression of cells having higher affinity receptors under circumstances in which T cell are relatively depleted or overstimulated, and further permits an explanation for the decrease of antibody affinity after long-term immunization.

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