Peripheral Innate Lymphoid Cells Are Increased in First Line Metastatic Colorectal Carcinoma Patients: A Negative Correlation With Th1 Immune Responses

Several distinct innate lymphoid cell (ILC) populations have been recently identified and shown to play a critical role in the immediate immune defense. In the context of tumors, there is evidence to support a dual role for ILCs with pro- or antitumor effects, depending on the ILC subset and the type of cancer. This ambivalent role has been particularly well described in colorectal cancer models (CRC), but the presence and the evolution of ILCs in the peripheral blood of metastatic CRC (mCRC) patients have not yet been explored. Here, we investigated the distribution of ILC subsets in 96 mCRC patients who were prospectively included in the ‘Epitopes-CRC02’ trial. Peripheral blood mononuclear cells were analyzed by flow cytometry at metastatic diagnosis and after 3-months of treatment. The treatments consisted of Oxaliplatin-based chemotherapies for 76% of the patients or Folfiri (5FU, Irinotecan) chemotherapies for 14% of patients. Compared to healthy donors, the frequency of total ILCs was dramatically increased at metastatic diagnosis. CD56+ ILC1-like cells were expanded, whereas ILC2, NCR- ILC3 and NCR+ ILC3 subsets were decreased. Combined analysis with the systemic anti-telomerase hTERT Th1 CD4 response revealed that patients with low anti-TERT Th1 CD4 responses had the highest frequencies of total ILCs at diagnosis. Of those, 91% had synchronous metastases, and their median progression-free survival was 7.43 months (vs. 9.17 months for the other patients). I...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

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ConclusionWe report the identification of dinactin as a natural product-based small molecule that effectively blocks the Wnt/ β-catenin signaling pathway in cancer cells at nano-molar concentration. We anticipate that DA could be developed as a novel drug for anti-cancer therapy and for the management of neuropathic pain.
Source: Cancer Chemotherapy and Pharmacology - Category: Cancer & Oncology Source Type: research
Patients Selection for Immunotherapy in Solid Tumors: Overcome the Naïve Vision of a Single Biomarker. Biomed Res Int. 2019;2019:9056417 Authors: Signorelli D, Giannatempo P, Grazia G, Aiello MM, Bertolini F, Mirabile A, Buti S, Vasile E, Scotti V, Pisapia P, Cona MS, Rolfo C, Malapelle U, Group IY Abstract Immunotherapy, and in particular immune-checkpoints blockade therapy (ICB), represents a new pillar in cancer therapy. Antibodies targeting Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) and Programmed Death 1 (PD-1)/Programmed Death Ligand-1 (PD-L1) demonstrated a relevant clinical value in a larg...
Source: Biomed Res - Category: Research Authors: Tags: Biomed Res Int Source Type: research
Discussion MDSCs violently emerge in pathological conditions in an attempt to limit potentially harmful immune and inflammatory responses. Mechanisms supporting their expansion and survival are deeply investigated in cancer, in the perspective to reactivate specific antitumor responses and prevent their contribution to disease evolution. These findings will likely contribute to improve the targeting of MDSCs in anticancer immunotherapies, either alone or in combination with immune checkpoint inhibitors. New evidence indicates that the expansion of myeloid cell differentiation in pathology is subject to fine-tuning, as its...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusions: We found a highly reliable FI network, which revealed LIFR, PIK3R1, and MMP12 as novel prognostic biomarker candidates for GBC. These findings could accelerate biomarker discovery and therapeutic development in this cancer. Introduction Gallbladder cancer (GBC), the sixth most common gastrointestinal cancer, is an uncommon but challenging disease. Its incidence has recently increased highly worldwide (1). The risk factors for GBC include sex, aging, obesity, chronic cholecystitis, and cholelithiasis (2, 3). Because of the lack of an effective early diagnostic method, the disease often is not diagnosed ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Michal Yalon1†, Amos Toren1,2†, Dina Jabarin2, Edna Fadida3, Shlomi Constantini3 and Ruty Mehrian-Shai1* 1Pediatric Hemato-Oncology, Edmond and Lilly Safra Children's Hospital and Cancer Research Center, Sheba Medical Center, Ramat Gan, Israel 2The Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel 3Department of Pediatric Neurosurgery, Dana Children's Hospital, Tel-Aviv-Sourasky Medical Center, Tel Aviv, Israel Pediatric brain tumors are the most common solid tumor type and the leading cause of cancer-related death in children. The immune system plays an important r...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusions This review describes how leukocyte-heparanase can be a double-edged sword in tumor progression; it can enhance tumor immune surveillance and tumor cell clearance, but also promote tumor survival and growth. We also discuss the potential of using heparanase in leukocyte therapies against tumors, and the effects of heparanase inhibitors on tumor progression and immunity. We are just beginning to understand the influence of heparanase on a pro/anti-tumor immune response, and there are still many questions to answer. How do the pro/anti-tumorigenic effects of heparanase differ across different cancer types? Does...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In conclusion, e-As4S4 holds great potential for an alternative therapeutics in the treatment of breast cancer, due to its unique function of correcting the aggressive microenvironment. Introduction Metastasis is the leading cause of breast cancer mortality, which has been one major challenge in clinical treatment (1). In particular, triple-negative breast cancer (TNBC) is characterized by the absence of estrogen receptors (ER), progesterone receptors (PR) and HER2 receptors, which is one of the most aggressive types of breast cancers, marked by high rates of relapse, visceral metastases and early death (2, 3). The...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
This study protocol was approved by the Institutional Review Board of the hospital. Data Collection Demographic and clinical data were retrieved from medical records in the hospital’s centralized database. These data included the age at diagnosis, International Federation of Obstetrics and Gynecologic (FIGO) stage, tumor histology and grade, type of surgery, and types and cycles of chemotherapy. Disease staging was based on the 2014 FIGO staging system. Optimal debulking surgery was defined as residual tumors with maximal diameters less than 1 cm; the others were defined as suboptimal debulking surgery. Disease rec...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Saeed Nourmohammadi1†, Thazin Nwe Aung2†, Jian Cui2, Jinxin V. Pei1, Michael Lucio De Ieso1, Yuka Harata-Lee2, Zhipeng Qu2, David L. Adelson2* and Andrea J. Yool1* 1Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia 2Department of Molecular and Biomedical Science, School of Biological Sciences, The University of Adelaide, Adelaide, SA, Australia Traditional Chinese Medicines are promising sources of new agents for controlling cancer metastasis. Compound Kushen Injection (CKI), prepared from medicinal plants Sophora flavescens and Heterosmilax chinensis, disrupts cell cycle...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In this report, we are adding an extra finding, in which we show that the levels of circulating NRP-1 were significantly increased in patients who received NAC and had a partial response. Assessing patients who underwent NAC indicated that the levels of NRP-1 measured post-NAC were significantly higher in younger patients and patients with either a low or a medium body mass index (BMI), as well as in patients who remained with larger tumor size and partial response. Previously, we showed that SNAI1 expression in the immune cells collected from the peripheral blood of breast cancer patients was significantly higher in patie...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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