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Immunocyto/Histochemistry in the Era of Immunotherapy
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Immunocyto/Histochemistry in the Era of Immunotherapy

A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Clinical Medicine, Cell, and Organism Physiology".

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 8026

Special Issue Editors

Dr. Ilaria Grazia Zizzari

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Guest Editor
Department of Experimental Medicine, “Sapienza” University of Rome, Viale Regina Elena, 324-00161 Rome, Italy
Interests: immunotherapy; cancer biology; cell therapy
Dr. Ilary Ruscito

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Guest Editor
Department of Medical and Surgical Sciences and Translational Medicine, Sapienza University of Rome, 324-00161 Rome, Italy
Interests: monoclonal antibodies; cancer cells; gynecology; tumors; antigen; gynaecology
Prof. Dr. A. Rughetti

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Guest Editor
Department of Experimental Medicine, “Sapienza” University of Rome, Viale Regina Elena, 324-00161 Rome, Italy
Interests: tumor immunolgoy; cancer immunotherapy; MUC1; antigen processing; antigen presentation; dendritic cells; glycoantigen; immune response

Special Issue Information

Dear Colleagues

This Special Issue is dedicated to the application of immunocytochemistry/histochemistry to characterize the tumor microenvironment in an immunotherapy context.

Immunotherapy in oncology is a breakthrough in the treatment of cancer. Treatment of cancer with immune checkpoint inhibitors (ICI) capable of unleashing T cells to exponentially expand and kill transformed cells, is the most recent and appealing treatment strategy being developed in the last decade. ICIs have been improving the survival of cancer patients. Nevertheless, not all patients respond and some of them show severe autoimmune toxicities and only 20–30% of treated patients present long term benefits. It is compelling to validate predictive and prognostic biomarkers to identify patients who are most likely to benefit from immunotherapy upfront and those who need to integrate/combine the immune-treatment with other strategies that can synergize the otherwise useless immunotherapy treatment. While some predictive factors of response to ICIs have been proposed, including PD-L1 expression, high tumor mutational burden, and mismatch repair gene defects, reliable biomarkers for the resistance to treatment are still lacking. This is in part due to the complexity of the tumor immune microenvironment and its impact on the immune drug efficacy.

How can pathologists identify predictive biomarkers to help to characterize individual responses to therapy and design customized treatments? The research of biomarkers of pathologic specimens to predict responses to therapy remains one of the key roles for pathologists in precision medicine.

Original manuscripts, review articles, and short communications are invited. Papers with promising potential applications, studies with results that are useful for unveiling immune mechanisms related to clinical responses, and applications of novel methodologies of imaging are particularly welcome.

You are cordially invited to submits contributions on this theme or related research topics to improve the immunocytochemistry knowledge of the tumor microenvironment and its correlation with clinical outcome.

Dr. Ilaria Grazia Zizzari
Dr. Ilary Ruscito
Prof. Dr. A. Rughetti
Guest Editors

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. Journal of Personalized Medicine 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 2600 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

  • Immune system/cells
  • Tumor microenvironment
  • Immunotherapy
  • ICI resistance
  • Immunocytochemistry
  • Immune receptors
  • Biomarker

Published Papers (2 papers)

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Research

11 pages, 1363 KiB  
Article
The Role of Soluble LAG3 and Soluble Immune Checkpoints Profile in Advanced Head and Neck Cancer: A Pilot Study
by Andrea Botticelli, Ilaria Grazia Zizzari, Simone Scagnoli, Giulia Pomati, Lidia Strigari, Alessio Cirillo, Bruna Cerbelli, Alessandra Di Filippo, Chiara Napoletano, Fabio Scirocchi, Aurelia Rughetti, Marianna Nuti, Silvia Mezi and Paolo Marchetti
J. Pers. Med. 2021, 11(7), 651; https://doi.org/10.3390/jpm11070651 - 10 Jul 2021
Cited by 28 | Viewed by 3065
Abstract
Unresectable recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) has a very poor prognosis. Soluble immune checkpoints (sICs) are circulating proteins that result from the alternative splicing of membrane proteins and can modulate the immune response to cancer cells. The [...] Read more.
Unresectable recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) has a very poor prognosis. Soluble immune checkpoints (sICs) are circulating proteins that result from the alternative splicing of membrane proteins and can modulate the immune response to cancer cells. The aim of our pilot study was to determine the possible role of a comprehensive evaluation of sICs in the classification of prognosis and response to treatment in patients with advanced disease. We evaluated several sICs (CD137, CTLA-4, PD-1, PD-L1, PD-L2, TIM3, LAG3, GITR, HVEM, BTLA, IDO, CD80, CD27, and CD28) from peripheral blood at baseline and investigated the association with clinical characteristics and outcomes. A high baseline soluble LAG3 (sLAG3 > 377 pg/mL) resulted in an association with poor PFS and OS (p = 0.047 and p = 0.003, respectively). Moreover, sLAG3 emerged as an independent prognostic factor using an MVA (p = 0.005). The evaluation of sICs, in particular sLAG3, may be relevant for identifying patients with worse prognoses, or resistance to treatments, and may lead to the development of novel targeted strategies. Full article
(This article belongs to the Special Issue Immunocyto/Histochemistry in the Era of Immunotherapy)
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16 pages, 2483 KiB  
Article
Immunohistochemical Characterization of Immune Infiltrate in Tumor Microenvironment of Glioblastoma
by Hassan Rahimi Koshkaki, Simone Minasi, Alessio Ugolini, Gianluca Trevisi, Chiara Napoletano, Ilaria G. Zizzari, Marco Gessi, Felice Giangaspero, Annunziato Mangiola, Marianna Nuti, Francesca R. Buttarelli and Aurelia Rughetti
J. Pers. Med. 2020, 10(3), 112; https://doi.org/10.3390/jpm10030112 - 03 Sep 2020
Cited by 19 | Viewed by 4292
Abstract
Background: Glioblastoma (GBM) is the most common primary malignant brain cancer in adults, with very limited therapeutic options. It is characterized by a severe immunosuppressive milieu mostly triggered by suppressive CD163+ tumor-associated macrophages (TAMs). The efficacy of immune checkpoint inhibitor interventions aimed [...] Read more.
Background: Glioblastoma (GBM) is the most common primary malignant brain cancer in adults, with very limited therapeutic options. It is characterized by a severe immunosuppressive milieu mostly triggered by suppressive CD163+ tumor-associated macrophages (TAMs). The efficacy of immune checkpoint inhibitor interventions aimed at rescuing anti-tumor immunity has not been proved to date. Thus, it is critically important to investigate the immunomodulatory mechanisms acting within the GBM microenvironment for the better design of immunotherapeutic strategies. Methods: The immunohistochemical analysis of a panel of immune biomarkers (CD3, FoxP3, CD163, IDO, PDL-1, PD-1 and TIGIT) was performed in paired samples of the tumor core (TC) and peritumoral area (PTA) of nine GBM patients. Results: CD163+ cells were the most common cell type in both the PTA and TC. IDO and PDL-1 were expressed in most of the TC samples, frequently accompanied by TIGIT expression; on the contrary, they were almost absent in the PTA. CD3+ cells were present in both the TC and PTA, to a lesser extent than CD163+ cells; they often were accompanied by PD-1 expression, especially in the TC. FoxP3 was scarcely present. Conclusion: Distinct inhibitory mechanisms can act simultaneously in both the TC and PTA to contribute to the strong immunosuppression observed within the GBM microenvironment. Nevertheless, the PTA shows strongly reduced immunosuppression when compared to the TC, thus representing a potential target for immunotherapies. Moreover, our results support the working hypothesis that immunosuppression and T-cell exhaustion can be simultaneously targeted to rescue anti-tumor immunity in GBM patients. Full article
(This article belongs to the Special Issue Immunocyto/Histochemistry in the Era of Immunotherapy)
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