Special Issue "Signaling Pathways and Immune Checkpoint Regulation in Cancer"

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (31 March 2019)

Special Issue Editor

Guest Editor
Prof. Dr. Georgios Rassidakis

Karolinska University Hospital, Department of Pathology and Cytology, Stockholm, Sweden
Website | E-Mail
Interests: lymphoma, leukemia, cancer signaling pathways, immune checkpoint regulation, oncogenes, tumor suppressor genes, transcription factors, targeted therapy, cancer biomarkers

Special Issue Information

Dear colleagues,

Intensive research over the last decades has uncovered the dynamic interactions between cancer cells and host immune cells, namely T-lymphocytes, NK cells, dendritic cells and histiocytes. The immune checkpoint plays a crucial role in the immune response against tumor cells, and therefore, better understanding of the underlying mechanisms led to the development of novel immunotherapeutic approaches in cancer. The basic concept of immunotherapy is that the target molecule is on the immune cell and not on the tumor cell, and therefore the same strategy would work on many different cancer cell types with different phenotype and genetic backgrounds. Immune checkpoint therapy initially focused on CTLA-4 with promising results. More recently, the PD-1 (programmed death-1) and its ligand (PD-L1) have been targeted with anti-PD-1 and anti-PD-L1 antibodies, which are currently being tested in clinical trials in a variety of cancers with clinical success. In certain tumor types, immunotherapy efficiency has been associated with PD-L1 protein levels. PD-L1 expression can be regulated at the genetic (e.g. PD-L1 gene amplification), transcriptional and post-translational level, however, the exact mechanisms may be cell type-specific and they are still under investigation. Transcription factors, known to regulate PD-L1 gene expression, commonly operate as targets of known oncogenic signaling pathways, thus providing the biologic rationale for combination treatment strategies such as immunotherapy with targeted therapy.

This Special Issue focuses on the mechanisms of immune checkpoint regulation by oncogenic signaling pathways that may represent novel therapeutic targets, as well as the role of the tumor microenvironment. In addition, immunotherapy-related studies including PD-1/PD-L1 antibodies and CART-T cell therapy are most welcome for publication consideration in this issue.

Prof. Dr. Georgios Rassidakis
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 papers will be 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 monthly 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 1800 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.


  • signaling pathways
  • immune checkpoint regulation
  • CTLA-4
  • PD-L1
  • CART-T cell therapy
  • immunotherapy
  • targeted therapy
  • transcription factors

Published Papers (1 paper)

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Open AccessReview Immunotherapy Associated Pulmonary Toxicity: Biology Behind Clinical and Radiological Features
Cancers 2019, 11(3), 305; https://doi.org/10.3390/cancers11030305
Received: 16 January 2019 / Revised: 17 February 2019 / Accepted: 26 February 2019 / Published: 5 March 2019
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The broader use of immune checkpoint blockade in clinical routine challenges clinicians in the diagnosis and management of side effects which are caused by inflammation generated by the activation of the immune response. Nearly all organs can be affected by immune-related toxicities. However, [...] Read more.
The broader use of immune checkpoint blockade in clinical routine challenges clinicians in the diagnosis and management of side effects which are caused by inflammation generated by the activation of the immune response. Nearly all organs can be affected by immune-related toxicities. However, the most frequently reported are: fatigue, rash, pruritus, diarrhea, nausea/vomiting, arthralgia, decreased appetite and abdominal pain. Although these adverse events are usually mild, reversible and not frequent, an early diagnosis is crucial. Immune-related pulmonary toxicity was most frequently observed in trials of lung cancer and of melanoma patients treated with the combination of the anti-cytotoxic T lymphocyte antigen (CTLA)-4 and the anti-programmed cell death-1 (PD-1) antibodies. The most frequent immune-related adverse event in the lung is represented by pneumonitis due to the development of infiltrates in the interstitium and in the alveoli. Clinical symptoms and radiological patterns are the key elements to be considered for an early diagnosis, rendering the differential diagnosis crucial. Diagnosis of immune-related pneumonitis may imply the temporary or definitive suspension of immunotherapy, along with the start of immuno-suppressive treatments. The aim of this work is to summarize the biological bases, clinical and radiological findings of lung toxicity under immune checkpoint blockade, underlining the importance of multidisciplinary teams for an optimal early diagnosis of this side effect, with the aim to reach an improved patient care. Full article
(This article belongs to the Special Issue Signaling Pathways and Immune Checkpoint Regulation in Cancer)

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