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Cancers
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Immunotherapy and Transplantation in the Era of Transplant Oncology
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Immunotherapy and Transplantation in the Era of Transplant Oncology

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Transplant Oncology".

Deadline for manuscript submissions: 31 August 2024 | Viewed by 15009

Special Issue Editors

Dr. Maen Abdelrahim

E-Mail Website
Guest Editor
1. Section of Gastrointestinal Oncology-Houston Methodist Cancer Center and Institute of Academic Medicine, 6445 Fannin, OPC-24, Houston, TX 77030, USA
2. Cockrell Center for Advanced Therapeutics (CCAT) – Phase I Program, Houston Methodist Research Institute, Houston, TX 77030, USA
3. Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
Interests: pancreatic cancer; liver cancer; cholangiocarcinoma; biliary cancer; transplant oncology; phase I drugs; targeted therapy; drug discovery; immunotherapy
Special Issues, Collections and Topics in MDPI journals
Dr. Ala Abudayyeh

E-Mail Website
Guest Editor
1. Section of Nephrology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
2.Director of Clinical Research, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Interests: onco-nephrology; transplant oncology; immunotherapy; immunotherapy toxicity; renal transplant
Dr. Abdullah Esmail

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Guest Editor
1. Section of Gastrointestinal Oncology - Houston Methodist Neal Cancer Center and Institute of Academic Medicine, 6445 Fannin, OPC-24, Houston, TX 77030, USA
2. Houston Methodist Research Institute, Houston, TX 77030, USA
Interests: transplant oncology; liver cancer; cholangiocarcinoma; targeted therapy; immunotherapy

Special Issue Information

Dear Colleagues,

Immune-checkpoint inhibitor (ICPI) therapies have shown excellent responses with tolerable side effects in the treatment of different cancers. However, our knowledge and experience in the use of immunotherapy in solid organ transplant recipients and candidates are limited.

The use of immunotherapy in liver pre-transplant patients as bridging therapy, and as palliative therapy in post-transplant patients to treat cancer recurrence or second primary cancer, is an area of unmet need. Transplant patients have been excluded from ICPI clinical trials due to concern for autograft rejection. In the last five years, retrospective studies and limited prospective trials have shown the possibility of using ICPIs in this patient population. This field of transplant oncology is currently being investigated. Our Special Issue will highlight the current state of the utilization of ICPI therapies in pre- and post-liver and other solid organ transplants, and will discuss the assessment of safety and response biomarkers. 

Dr. Maen Abdelrahim
Dr. Ala Abudayyeh
Dr. Abdullah Esmail
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

  • transplant oncology
  • liver transplantation
  • solid organ transplantation, hepatocellular carcinoma
  • immunotherapy
  • immune-checkpoint inhibitors
  • CTLA-4 inhibitors
  • PD-1 inhibitors
  • allograft rejection

Published Papers (7 papers)

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Research

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15 pages, 899 KiB  
Article
Impact of Infections in Patients Receiving Pembrolizumab-Based Therapies for Non-Small Cell Lung Cancer
by Ethan A. Burns, Kelly Gee, Ryan B. Kieser, Jiaqiong Xu, Yuqi Zhang, Aubrey Crenshaw, Ibrahim N. Muhsen, Charisma Mylavarapu, Abdullah Esmail, Shivan Shah, Godsfavour Umoru, Kai Sun, Carlo Guerrero, Zimu Gong, Kirk Heyne, Monisha Singh, Jun Zhang, Eric H. Bernicker and Maen Abdelrahim
Cancers 2023, 15(1), 81; https://doi.org/10.3390/cancers15010081 - 23 Dec 2022
Cited by 2 | Viewed by 2067
Abstract
Background: Immune checkpoint inhibitor (ICI) therapy has significantly improved outcomes across a range of malignancies. While infections are a well-known contributor to morbidity and mortality amongst patients receiving systemic chemotherapy regimens, little is known about the impact of infections on patients receiving ICI [...] Read more.
Background: Immune checkpoint inhibitor (ICI) therapy has significantly improved outcomes across a range of malignancies. While infections are a well-known contributor to morbidity and mortality amongst patients receiving systemic chemotherapy regimens, little is known about the impact of infections on patients receiving ICI therapy. This study aims to assess incidence, risk factors, and outcomes in patients who develop infections while on pembrolizumab-based therapies for non-small cell lung cancer (NSCLC). Methods: Patients receiving pembrolizumab for stage III/IV NSCLC from 1/1/2017-8/1/2021 across seven hospitals were identified. Incidence and type of infection were characterized. Covariates including baseline demographics, treatment information, treatment toxicities, and immunosuppressive use were collected and compared between infected and non-infected patients. Outcomes included the rate of infections, all-cause hospital admissions, median number of treatment cycles, overall survival (OS), and progression free survival (PFS). Univariable and multivariable analysis with reported odds ratio (OR) and 95% confidence intervals (CI) were utilized to evaluate infection risks. OS and PFS were analyzed by Kaplan–Meier analysis and tested by log-rank test. p-value < 0.05 was considered statistically significant. Results: There were 243 NSCLC patients that met the inclusion criteria. Of these, 111 (45.7%) had one documented infection, and 36 (14.8%) had two or more. Compared to non-infected patients, infected patients had significantly more all-cause Emergency Department (ED) [37 (33.3%) vs. 26 (19.7%), p = 0.016], hospital [87 (78.4%) vs. 53 (40.1%), p < 0.001], and ICU visits [26 (23.4%) vs. 5 (3.8%), p < 0.001], and had poorer median OS (11.53 [95% CI 6.4–16.7] vs. 21.03 [95% CI: 14.7–24.2] months, p = 0.033). On multivariable analysis, anti-infective therapy (OR 3.32, [95% CI: 1.26–8.76], p = 0.015) and ECOG of >1 (OR 5.79, [95% CI 1.72–19.47], p = 0.005) at ICI initiation conferred an increased risk for infections. At last evaluation, 74 (66.7%) infected and 70 (53.0%) non-infected patients died (p = 0.041). Conclusion: Infections occurred in nearly half of patients receiving pembrolizumab-based therapies for NSCLC. Infected patients had frequent hospitalizations, treatment delays, and poorer survival. ECOG status and anti-infective use at ICI initiation conferred a higher infection risk. Infection prevention and control strategies are needed to ameliorate the risk for infections in patients receiving ICIs. Full article
(This article belongs to the Special Issue Immunotherapy and Transplantation in the Era of Transplant Oncology)
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Review

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25 pages, 1937 KiB  
Review
Transplant Oncology: An Emerging Discipline of Cancer Treatment
by Maen Abdelrahim, Abdullah Esmail, Ala Abudayyeh, Naoka Murakami, David Victor, Sudha Kodali, Yee Lee Cheah, Caroline J. Simon, Mazen Noureddin, Ashton Connor, Ashish Saharia, Linda W. Moore, Kirk Heyne, Ahmed O. Kaseb, A. Osama Gaber and Rafik Mark Ghobrial
Cancers 2023, 15(22), 5337; https://doi.org/10.3390/cancers15225337 - 09 Nov 2023
Viewed by 1551
Abstract
Transplant oncology is an emerging concept of cancer treatment with a promising prospective outcome. The applications of oncology, transplant medicine, and surgery are the core of transplant oncology to improve patients’ survival and quality of life. The main concept of transplant oncology is [...] Read more.
Transplant oncology is an emerging concept of cancer treatment with a promising prospective outcome. The applications of oncology, transplant medicine, and surgery are the core of transplant oncology to improve patients’ survival and quality of life. The main concept of transplant oncology is to radically cure cancer by removing the diseased organ and replacing it with a healthy one, aiming to improve the survival outcomes and quality of life of cancer patients. Subsequently, it seeks to expand the treatment options and research for hepatobiliary malignancies, which have seen significantly improved survival outcomes after the implementation of liver transplantation (LT). In the case of colorectal cancer (CRC) in the transplant setting, where the liver is the most common site of metastasis of patients who are considered to have unresectable disease, initial studies have shown improved survival for LT treatment compared to palliative therapy interventions. The indications of LT for hepatobiliary malignancies have been slowly expanded over the years beyond Milan criteria in a stepwise manner. However, the outcome improvements and overall patient survival are limited to the specifics of the setting and systematic intervention options. This review aims to illustrate the representative concepts and history of transplant oncology as an emerging discipline for the management of hepatobiliary malignancies, in addition to other emerging concepts, such as the uses of immunotherapy in a peri-transplant setting as well as the use of circulating tumor DNA (ctDNA) for surveillance post-transplantation. Full article
(This article belongs to the Special Issue Immunotherapy and Transplantation in the Era of Transplant Oncology)
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14 pages, 267 KiB  
Review
Hepatocellular Carcinoma: The Role of Immunotherapy and Transplantation in the Era of Transplant Oncology
by Saad Alghamdi and Waleed Al-Hamoudi
Cancers 2023, 15(21), 5115; https://doi.org/10.3390/cancers15215115 - 24 Oct 2023
Viewed by 1183
Abstract
Hepatocellular carcinoma (HCC) is one of the most common causes of cancer deaths worldwide. As most patients present with advanced disease, curative therapy such as surgical resection and radiofrequency ablation are rarely utilized. With the advent of immunotherapy, historical treatment approaches such as [...] Read more.
Hepatocellular carcinoma (HCC) is one of the most common causes of cancer deaths worldwide. As most patients present with advanced disease, curative therapy such as surgical resection and radiofrequency ablation are rarely utilized. With the advent of immunotherapy, historical treatment approaches such as liver transplantation are being challenged. In particular, the use of immune checkpoint inhibitors (ICIs) has emerged as a safe and useful option in the treatment of HCC. However, there is concern over adverse effects, such as graft rejection and graft loss. This updated review discusses the role of immunotherapy in the pre- and post-transplantation setting and provides insights into the potential of immunotherapy as an adjunct to liver transplantation. We deliberate on the use of ICI in the setting of the Milan criteria as well as the University of California San Francisco’s expanded criteria for liver transplantation. Current data suggest that ICI has utility, especially in the pretransplantation setting. Nevertheless, larger, purposefully designed clinical trials are needed to clearly identify patients who will benefit most from ICI treatment in the transplant setting and determine parameters that will minimize the risk of graft rejection and maximize the benefits of this adjunct treatment. Full article
(This article belongs to the Special Issue Immunotherapy and Transplantation in the Era of Transplant Oncology)
19 pages, 1779 KiB  
Review
Immunotherapy and Liver Transplantation: A Narrative Review of Basic and Clinical Data
by Charles-Henri Wassmer, Sofia El Hajji, Xenofon Papazarkadas, Philippe Compagnon, Parissa Tabrizian, Stéphanie Lacotte and Christian Toso
Cancers 2023, 15(18), 4574; https://doi.org/10.3390/cancers15184574 - 15 Sep 2023
Cited by 4 | Viewed by 1364
Abstract
Immune checkpoint inhibitors (ICIs) have improved the management of patients with intermediate- and advanced-stage HCC, even making some of them potential candidates for liver transplantation. However, acute rejection has been observed after ICI therapy, challenging its safety in transplant settings. We summarize the [...] Read more.
Immune checkpoint inhibitors (ICIs) have improved the management of patients with intermediate- and advanced-stage HCC, even making some of them potential candidates for liver transplantation. However, acute rejection has been observed after ICI therapy, challenging its safety in transplant settings. We summarize the key basic impact of immune checkpoints on HCC and liver transplantation. We analyze the available case reports and case series on the use of ICI therapy prior to and after liver transplantation. A three-month washout period is desirable between ICI therapy and liver transplantation to reduce the risk of acute rejection. Whenever possible, ICIs should be avoided after liver transplantation, and especially so early after a transplant. Globally, more robust prospective data in the field are required. Full article
(This article belongs to the Special Issue Immunotherapy and Transplantation in the Era of Transplant Oncology)
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32 pages, 725 KiB  
Review
Immune Checkpoint Inhibitors for Solid Tumors in the Adjuvant Setting: Current Progress, Future Directions, and Role in Transplant Oncology
by Karen Abboud, Godsfavour Umoru, Abdullah Esmail, Ala Abudayyeh, Naoka Murakami, Humaid O. Al-Shamsi, Milind Javle, Ashish Saharia, Ashton A. Connor, Sudha Kodali, Rafik M. Ghobrial and Maen Abdelrahim
Cancers 2023, 15(5), 1433; https://doi.org/10.3390/cancers15051433 - 23 Feb 2023
Cited by 4 | Viewed by 3552
Abstract
The rationale for administering immune checkpoint inhibitors (ICIs) in the adjuvant setting is to eradicate micro-metastases and, ultimately, prolong survival. Thus far, clinical trials have demonstrated that 1-year adjuvant courses of ICIs reduce the risk of recurrence in melanoma, urothelial cancer, renal cell [...] Read more.
The rationale for administering immune checkpoint inhibitors (ICIs) in the adjuvant setting is to eradicate micro-metastases and, ultimately, prolong survival. Thus far, clinical trials have demonstrated that 1-year adjuvant courses of ICIs reduce the risk of recurrence in melanoma, urothelial cancer, renal cell carcinoma, non-small cell lung cancer, and esophageal and gastroesophageal junction cancers. Overall survival benefit has been shown in melanoma while survival data are still not mature in other malignancies. Emerging data also show the feasibility of utilizing ICIs in the peri-transplant setting for hepatobiliary malignancies. While ICIs are generally well-tolerated, the development of chronic immune-related adverse events, typically endocrinopathies or neurotoxicities, as well as delayed immune-related adverse events, warrants further scrutiny regarding the optimal duration of adjuvant therapy and requires a thorough risk–benefit determination. The advent of blood-based, dynamic biomarkers such as circulating tumor DNA (ctDNA) can help detect minimal residual disease and identify the subset of patients who would likely benefit from adjuvant treatment. In addition, the characterization of tumor-infiltrating lymphocytes, neutrophil-to-lymphocyte ratio, and ctDNA-adjusted blood tumor mutation burden (bTMB) has also shown promise in predicting response to immunotherapy. Until additional, prospective studies delineate the magnitude of overall survival benefit and validate the use of predictive biomarkers, a tailored, patient-centered approach to adjuvant ICIs that includes extensive patient counseling on potentially irreversible adverse effects should be routinely incorporated into clinical practice. Full article
(This article belongs to the Special Issue Immunotherapy and Transplantation in the Era of Transplant Oncology)
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27 pages, 745 KiB  
Review
Recent Trends and Advancements in the Diagnosis and Management of Gastric Cancer
by Emaan Haque, Abdullah Esmail, Ibrahim Muhsen, Haneen Salah and Maen Abdelrahim
Cancers 2022, 14(22), 5615; https://doi.org/10.3390/cancers14225615 - 15 Nov 2022
Cited by 10 | Viewed by 1951
Abstract
Gastric cancer is an enigmatic malignancy that has recently been shown to be increasing in incidence globally. There has been recent progress in emerging technologies for the diagnosis and treatment of the disease. Improvements in non-invasive diagnostic techniques with serological tests and biomarkers [...] Read more.
Gastric cancer is an enigmatic malignancy that has recently been shown to be increasing in incidence globally. There has been recent progress in emerging technologies for the diagnosis and treatment of the disease. Improvements in non-invasive diagnostic techniques with serological tests and biomarkers have led to decreased use of invasive procedures such as endoscopy. A multidisciplinary approach is used to treat gastric cancer, with recent significant advancements in systemic therapies used in combination with cytotoxic chemotherapies. New therapeutic targets have been identified and clinical trials are taking place to assess their efficacy and safety. In this review, we provide an overview of the current and emerging treatment strategies and diagnostic techniques for gastric cancer. Full article
(This article belongs to the Special Issue Immunotherapy and Transplantation in the Era of Transplant Oncology)
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21 pages, 2457 KiB  
Review
Newest Therapies for Cholangiocarcinoma: An Updated Overview of Approved Treatments with Transplant Oncology Vision
by Yuqi Zhang, Abdullah Esmail, Vincenzo Mazzaferro and Maen Abdelrahim
Cancers 2022, 14(20), 5074; https://doi.org/10.3390/cancers14205074 - 17 Oct 2022
Cited by 9 | Viewed by 2569
Abstract
A minority of cholangiocarcinoma (CCA) can be cured by surgical intervention (i.e., liver resection (LR) and liver transplantation (LT)). When modern criteria for LT are met, this intervention along with neoadjuvant treatments may achieve unprecedented survival in selected patients. Liver resection is associated [...] Read more.
A minority of cholangiocarcinoma (CCA) can be cured by surgical intervention (i.e., liver resection (LR) and liver transplantation (LT)). When modern criteria for LT are met, this intervention along with neoadjuvant treatments may achieve unprecedented survival in selected patients. Liver resection is associated with a median overall survival (OS) of 40 months, this number drastically decreases for unresectable advanced cholangiocarcinoma (CCA), which is treated with systemic therapy. The first-line chemotherapy regimen of gemcitabine and cisplatin is associated with a median overall survival of only 11.7 months. Since the Food and Drug Administration (FDA)’s approval of the isocitrate dehydrogenase (IDH) 1 inhibitor ivosidenib in August 2021, there has been increasing interest in targeted therapy for CCA patients harboring mutations in fibroblast growth factor receptor (FGFR) 2, neurotrophic receptor tyrosine kinase (NTRK), B-raf kinase (BRAF), and HER2. At the same time, immunotherapy with immune checkpoint inhibitors isalso being used in relapsed CCA. This review looks into the most recently completed and ongoing studies of targeted therapy as monotherapy or in combination with chemo- and/or immunotherapy. Whether it is resection, liver transplant, radiotherapy, chemotherapy, immunotherapy, targeted therapy, or any combination of these treatment modalities, great strides are being made to improve outcomes for this challenging disease. Full article
(This article belongs to the Special Issue Immunotherapy and Transplantation in the Era of Transplant Oncology)
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