State-of-the-Art Cancer Immunology and Immunotherapy in the USA

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

Deadline for manuscript submissions: 20 June 2024 | Viewed by 7305

Special Issue Editors


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Guest Editor
Froedtert & The Medical College of Wisconsin Clinical Cancer Center, Milwaukee, WI 53226, USA
Interests: rare diseases; immunotherapy; precision oncology
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Guest Editor
Division of Medical Oncology, Department of Medicine, Kansas University Cancer Center, Westwood, KS 66205, USA
Interests: immune checkpoints; checkpoint inhibitors; immunotherapy; tumor immunology; tumor vaccines
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Interests: cancer; therapy; signaling pathway; HER; EGF; Wnt; notch; TGF-β; mTOR; PD-1/PD-L1
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA
Interests: developmental therapeutics; molecularly targeted agents; epigenetic modifiers; small molecule inhibitors; immune-oncology; bispecifics; T-cell engagers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cancer remains the top public health burden worldwide. In the United States, an estimated number of new cancer cases is 1,918,030, and 609,360 estimated deaths cases of cancer in 2022. The leading cause of death is lung cancer, with about 350 losses of lives per day. Immunotherapy of cancer has become an important daily clinical practice of cancer treatment in recent decades. However, the partial response from patients, treatment resistance, metastasis, adverse side effects, and even high cost are remaining major concerns during the therapeutic period. These are the urgent issues that need to be overcome.

The aim of this Special Issue is to collect high-quality basic research, preclinical research, and clinical research on cancer immunology and immunotherapy articles conducted in the United States or by researchers affiliated and/or cooperated with researchers in the United States.

We hope that this Special Issue will highlight state-of-the-art cancer immunology and immunotherapy and promote and raise novel therapeutic strategies against cancer in the USA and worldwide. 

Prof. Dr. Razelle Kurzrock
Dr. Anwaar Saeed
Dr. Linlin Guo
Dr. Ludimila Cavalcante
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. 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

  • cancer research
  • immune system
  • immunology
  • immunotherapy
  • CAR T-cell therapy
  • checkpoint inhibitor
  • monoclonal antibody
  • cancer cellular signaling
  • tumor microenvironment
  • combination therapy

Published Papers (4 papers)

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Research

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12 pages, 927 KiB  
Article
Characterization of Age-Associated, Neutrophil-to-Lymphocyte Ratio (NLR) and Systemic Immune-Inflammatory Index (SII) as Biomarkers of Inflammation in Geriatric Patients with Cancer Treated with Immune Checkpoint Inhibitors: Impact on Efficacy and Survival
by Khalil Choucair, Caroline Nebhan, Alessio Cortellini, Stijn Hentzen, Yinghong Wang, Cynthia Liu, Raffaele Giusti, Marco Filetti, Paolo Antonio Ascierto, Vito Vanella, Domenico Galetta, Annamaria Catino, Nour Al-Bzour, Azhar Saeed, Ludimila Cavalcante, Pamela Pizzutilo, Carlo Genova, Melissa Bersanelli, Sebastiano Buti, Douglas B. Johnson, Claudia Angela Maria Fulgenzi, David J. Pinato, Maluki Radford, Chul Kim, Abdul Rafeh Naqash and Anwaar Saeedadd Show full author list remove Hide full author list
Cancers 2023, 15(20), 5052; https://doi.org/10.3390/cancers15205052 - 19 Oct 2023
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Abstract
Background: Geriatric patients (≥80 years) are underrepresented in immune checkpoint inhibitor (ICIs) clinical trials. However, their unique biology may affect their response to ICIs. There are currently no established biomarkers of the response to ICIs in adult patients with cancer that can help [...] Read more.
Background: Geriatric patients (≥80 years) are underrepresented in immune checkpoint inhibitor (ICIs) clinical trials. However, their unique biology may affect their response to ICIs. There are currently no established biomarkers of the response to ICIs in adult patients with cancer that can help with patient selection. Methods: We built a multicenter, international retrospective study of 885 patients (<80 years: n = 417, 47.12%; ≥80 years: n = 468, 52.88%) with different tumor types treated with ICIs between 2011 and 2021 from 11 academic centers in the U.S. and Europe. The main outcome measures were objective response rates (ORR), progression-free survival (PFS) and overall survival (OS) stratified by age and circulating inflammatory levels (neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammatory index (SII)). Results: Patients ≥80 years with low NLR (NLR-L) and SII (SII-L) had significantly higher ORR (vs. high NLR [NLR-H], p < 0.01 and SII-H, p < 0.05, respectively). At median follow-ups (13.03 months), and compared to SII-H, patients with SII-L had significantly longer median PFS and OS in patients <80 (p < 0.001), and ≥80 years (p < 0.001). SII-L was independently associated with longer PFS and OS (HR: 0.61 and 0.62, respectively, p < 0.01). Conclusion: Lower inflammation pre-ICI initiation may predict an improved response and survival in geriatric patients with cancer. Full article
(This article belongs to the Special Issue State-of-the-Art Cancer Immunology and Immunotherapy in the USA)
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20 pages, 3763 KiB  
Article
Genomic and Transcriptomic Predictors of Response to Immune Checkpoint Inhibitors in Melanoma Patients: A Machine Learning Approach
by Yaman B. Ahmed, Ayah N. Al-Bzour, Obada E. Ababneh, Hassan M. Abushukair and Anwaar Saeed
Cancers 2022, 14(22), 5605; https://doi.org/10.3390/cancers14225605 - 15 Nov 2022
Cited by 4 | Viewed by 2350
Abstract
Immune checkpoint inhibitors (ICIs) became one of the most revolutionary cancer treatments, especially in melanoma. While they have been proven to prolong survival with lesser side effects compared to chemotherapy, the accurate prediction of response remains to be an unmet gap. Thus, we [...] Read more.
Immune checkpoint inhibitors (ICIs) became one of the most revolutionary cancer treatments, especially in melanoma. While they have been proven to prolong survival with lesser side effects compared to chemotherapy, the accurate prediction of response remains to be an unmet gap. Thus, we aim to identify accurate clinical and transcriptomic biomarkers for ICI response in melanoma. We also provide mechanistic insight into how high-performing markers impose their effect on the tumor microenvironment (TME). Clinical and transcriptomic data were retrieved from melanoma studies administering ICIs from cBioportal and GEO databases. Four machine learning models were developed using random-forest classification (RFC) entailing clinical and genomic features (RFC7), differentially expressed genes (DEGs, RFC-Seq), survival-related DEGs (RFC-Surv) and a combination model. The xCELL algorithm was used to investigate the TME. A total of 212 ICI-treated melanoma patients were identified. All models achieved a high area under the curve (AUC) and bootstrap estimate (RFC7: 0.71, 0.74; RFC-Seq: 0.87, 0.75; RFC-Surv: 0.76, 0.76, respectively). Tumor mutation burden, GSTA3, and VNN2 were the highest contributing features. Tumor infiltration analyses revealed a direct correlation between upregulated genes and CD8+, CD4+ T cells, and B cells and inversely correlated with myeloid-derived suppressor cells. Our findings confirmed the accuracy of several genomic, clinical, and transcriptomic-based RFC models, that could further support the use of TMB in predicting response to ICIs. Novel genes (GSTA3 and VNN2) were identified through RFC-seq and RFC-surv models that could serve as genomic biomarkers after robust validation. Full article
(This article belongs to the Special Issue State-of-the-Art Cancer Immunology and Immunotherapy in the USA)
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Review

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26 pages, 2546 KiB  
Review
Overcoming Immune Checkpoint Therapy Resistance with SHP2 Inhibition in Cancer and Immune Cells: A Review of the Literature and Novel Combinatorial Approaches
by Alireza Tojjari, Anwaar Saeed, Arezoo Sadeghipour, Razelle Kurzrock and Ludimila Cavalcante
Cancers 2023, 15(22), 5384; https://doi.org/10.3390/cancers15225384 - 13 Nov 2023
Cited by 1 | Viewed by 1732
Abstract
SHP2 (Src Homology 2 Domain-Containing Phosphatase 2) is a protein tyrosine phosphatase widely expressed in various cell types. SHP2 plays a crucial role in different cellular processes, such as cell proliferation, differentiation, and survival. Aberrant activation of SHP2 has been implicated in multiple [...] Read more.
SHP2 (Src Homology 2 Domain-Containing Phosphatase 2) is a protein tyrosine phosphatase widely expressed in various cell types. SHP2 plays a crucial role in different cellular processes, such as cell proliferation, differentiation, and survival. Aberrant activation of SHP2 has been implicated in multiple human cancers and is considered a promising therapeutic target for treating these malignancies. The PTPN11 gene and functions encode SHP2 as a critical signal transduction regulator that interacts with key signaling molecules in both the RAS/ERK and PD-1/PD-L1 pathways; SHP2 is also implicated in T-cell signaling. SHP2 may be inhibited by molecules that cause allosteric (bind to sites other than the active site and attenuate activation) or orthosteric (bind to the active site and stop activation) inhibition or via potent SHP2 degraders. These inhibitors have anti-proliferative effects in cancer cells and suppress tumor growth in preclinical models. In addition, several SHP2 inhibitors are currently in clinical trials for cancer treatment. This review aims to provide an overview of the current research on SHP2 inhibitors, including their mechanism of action, structure-activity relationships, and clinical development, focusing on immune modulation effects and novel therapeutic strategies in the immune-oncology field. Full article
(This article belongs to the Special Issue State-of-the-Art Cancer Immunology and Immunotherapy in the USA)
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13 pages, 653 KiB  
Review
SLAM Modification as an Immune-Modulatory Therapeutic Approach in Cancer
by Alireza Tojjari, Francis J. Giles, Maysa Vilbert, Anwaar Saeed and Ludimila Cavalcante
Cancers 2023, 15(19), 4808; https://doi.org/10.3390/cancers15194808 - 29 Sep 2023
Cited by 1 | Viewed by 1463
Abstract
In the field of oncology, the Signaling Lymphocyte Activation Molecule (SLAM) family is emerging as pivotal in modulating immune responses within tumor environments. The SLAM family comprises nine receptors, mainly found on immune cell surfaces. These receptors play complex roles in the interaction [...] Read more.
In the field of oncology, the Signaling Lymphocyte Activation Molecule (SLAM) family is emerging as pivotal in modulating immune responses within tumor environments. The SLAM family comprises nine receptors, mainly found on immune cell surfaces. These receptors play complex roles in the interaction between cancer and the host immune system. Research suggests SLAM’s role in both enhancing and dampening tumor-immune responses, influencing the progression and treatment outcomes of various cancers. As immunotherapy advances, resistance remains an issue. The nuanced roles of the SLAM family might provide answers. With the rise in technologies like single-cell RNA sequencing and advanced imaging, there is potential for precise SLAM-targeted treatments. This review stresses patient safety, the importance of thorough clinical trials, and the potential of SLAM-focused therapies to transform cancer care. In summary, SLAM’s role in oncology signals a new direction for more tailored and adaptable cancer treatments. Full article
(This article belongs to the Special Issue State-of-the-Art Cancer Immunology and Immunotherapy in the USA)
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