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Immunotherapeutic Targets for Gastrointestinal Cancers

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (28 February 2022) | Viewed by 7081

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Special Issue Editor

Dr. Joanne Lysaght

E-Mail Website1 Website2
Guest Editor

1. Cancer Immunology and Immunotherapy Group, Department of Surgery, Trinity Translational Medicine Institute, Trinity College Dublin, St James’s Hospital, Dublin 8, Ireland
2. Trinity St James’s Cancer Institute, St James’s Hospital, Dublin 8, Ireland
Interests: upper gastrointestinal cancer; cancer immunology; immunotherapy; combination treatments; tumor microenvironment; treatment response

Special Issue Information

Dear Colleagues,

Gastrointestinal cancers are amongst the most common malignancies worldwide, and a major contributor to cancer-associated mortality rates. Traditionally, patients with GI cancers are treated with surgery, adjuvant or neoadjuvant chemotherapy, and/or radiotherapy, and, more recently, molecular targeted therapies. Over the last decade in particular, immunotherapy has begun to change the face of cancer treatment for so many patients, including GI patients, but response rates still remain disappointingly low. The focus has now turned to identifying novel immunotherapeutic targets, improving scheduling, and the incorporation of immunotherapies into standard of care regimens. In addition, there is significant interest in the identification of biomarkers indicative of treatment response, and primary or acquired resistance, with the ultimate goal of stratifying patients for treatment selection and improving the overall treatment response rates and outcomes. This Special Issue will see experts in the field highlight the recent advances in the exciting and rapidly evolving field of cancer immunotherapy for GI cancers.

Dr. Joanne Lysaght
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

immunotherapy
gastrointestinal cancers
biomarkers
novel targets
resistance
combination treatments

Published Papers (2 papers)

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Research

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16 pages, 2410 KiB

Open AccessArticle

The Transmembrane Receptor TIRC7 Identifies a Distinct Subset of Immune Cells with Prognostic Implications in Cholangiocarcinoma

by Thomas Albrecht, Benjamin Goeppert, Fritz Brinkmann, Alphonse Charbel, Qiangnu Zhang, Johannes Schreck, Nina Wilhelm, Stephan Singer, Bruno C. Köhler, Christoph Springfeld, Arianeb Mehrabi, Peter Schirmacher, Anja A. Kühl, Monika N. Vogel, Holger Jansen, Nalân Utku and Stephanie Roessler

Cancers 2021, 13(24), 6272; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13246272 - 14 Dec 2021

Cited by 1 | Viewed by 2078

Abstract

Cholangiocarcinoma (CCA) is a heterogeneous malignancy with a dismal prognosis. Therapeutic options are largely limited to surgery and conventional chemotherapy offers limited benefit. As immunotherapy has proven highly effective in various cancer types, we have undertaken a quantitative immunohistopathological assessment of immune cells expressing the immunoinhibitory T cell immune response cDNA 7 receptor (TIRC7), an emerging immunoinhibitory receptor, in a cohort of 135 CCA patients. TIRC7⁺ immune cells were present in both the tumor epithelia and stroma in the majority of CCA cases with the highest levels found in intrahepatic CCA. While intraepithelial density of TIRC7⁺ immune cells was decreased compared to matched non-neoplastic bile ducts, stromal quantity was higher in the tumor samples. Tumors exhibiting signet ring cell or adenosquamous morphology were exclusively associated with an intraepithelial TIRC7⁺ phenotype. Survival analysis showed intraepithelial TIRC7⁺ immune cell density to be a highly significant favorable prognosticator in intrahepatic but not proximal or distal CCA. Furthermore, intraepithelial TIRC7⁺ immune cell density correlated with the number of intraepithelial CD8⁺ immune cells and with the total number of CD4⁺ immune cells. Our results suggest the presence and prognostic relevance of TIRC7⁺ immune cells in CCA and warrant further functional studies on its pharmacological modulation. Full article

(This article belongs to the Special Issue Immunotherapeutic Targets for Gastrointestinal Cancers)

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Review

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14 pages, 1957 KiB

Open AccessReview

Combination Immunotherapies to Overcome Intrinsic Resistance to Checkpoint Blockade in Microsatellite Stable Colorectal Cancer

by Chang Woo Kim, Hong Jae Chon and Chan Kim

Cancers 2021, 13(19), 4906; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13194906 - 29 Sep 2021

Cited by 21 | Viewed by 4438

Abstract

Although immune checkpoint inhibitors (ICIs) have shown promising results in the treatment of treating various malignancies, progress has been severely limited in metastatic colorectal cancer (mCRC). ICIs are effective in a fraction of patients with microsatellite instability-high mCRC but have little clinical efficacy in patients with microsatellite stable (MSS) mCRC, which accounts for 95% of mCRC cases. MSS mCRCs are considered to have intrinsic resistance to ICI monotherapy through multiple mechanisms. (1) They are poorly immunogenic because of their low tumor mutation burden; (2) frequent activation of the WNT/β-catenin signaling pathway excludes intratumoral CD8⁺ T cell immunity; (3) the tumor microenvironment is immunosuppressive because of the presence of various immunosuppressive cells, including tumor-associated macrophages and regulatory T cells; and (4) frequent liver metastasis in MSS mCRC may reduce the efficacy of ICIs. To overcome these resistance mechanisms, combination approaches using various agents, including STING agonists, MEK inhibitors, VEGF/R inhibitors, WNT/β-catenin inhibitors, oncolytic viruses, and chemo/radiotherapy, are actively ongoing. Preliminary evidence of the efficacy of some has been shown in early clinical trials. This review summarizes novel combination immunotherapy strategies described in recent preclinical and clinical studies to overcome the limitations of ICI monotherapy in MSS mCRC. Full article

(This article belongs to the Special Issue Immunotherapeutic Targets for Gastrointestinal Cancers)

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