P02.01 T- and B-cell abundance are remarkably reduced in the immune microenvironment of post-transplant malignancies

BackgroundImmunosuppressive medication is mandatory in the majority of solid organ transplant recipients to reduce the risk of allograft rejection. An increased risk to develop cancer is a negative side effect of long-term immunosuppression and impaired cancer immunosurveillance is assumed as underlying mechanism. However, the impact of immunosuppression on the tumor immune microenvironment (TME) is poorly understood. In this study we aimed to elucidate differences between immune infiltrates of post-transplant malignancies and cancer of non-immunosuppressed patients.Materials and Methods117 resected tumor samples of 80 organ transplant (kidney, heart, lung and liver) recipients were included. Immunohistochemistry and digital image analysis of whole section slides was used to quantify T- (CD3, CD8) and B-cell (CD20) abundance in the TME of 14 different cancer types. These data were used to calculate the Immune-score and to quantify tertiary lymphoid structures in the TME. Expression of Human-Leucocyte-Antigen-I (HLA-I) and programmed cell death ligand 1 (PD-L1) were analyzed in tissue microarrays. Clinical parameters were included in statistical analyses.ResultsThe increased risk of cancer in organ transplant recipients was reflected by a remarkably reduced immune infiltrate in the central region (CT) and the surrounding tissue (invasive margin, IM) of cancer areas. T cell abundance was decreased in IM and CT of skin (814 vs. 1440 CD3+ cells/mm2, p < 0.01) and non-skin tumors (479 vs. 781 CD3+ cells/mm2, p < 0.01), when compared to non-immunosuppressed controls. These differences were more pronounced in the IM than in the CT and larger when comparing abundance of CD8+ T cells. The Immune-score integrating results from CT and IM was also decreased in transplant recipients. Similar to the results observed for T cells, B cell abundance and density of tertiary lymphoid structures were lower in cancer samples of transplant recipients. Decreased expression of HLA-I was more common in transplant recipients whereas the fraction of samples with PD-L1 expression was higher in controls.ConclusionsOur study demonstrates that post-transplant malignancies show a low immune infiltrate and supports the hypothesis of reduced anti-tumor immune response as an important mechanism underlying increased risk of cancer in organ transplant recipients. Optimized immunosuppressive protocols may be able to reduce cancer incidence and cancer therapies need to consider the distinct immune microenvironment of post-transplant malignancies.Disclosure InformationS. Schran: None. R. Datta: None. O. Persa: None. C. Aguilar: None. M. Thelen: None. J. Lehmann: None. M. Garcia-Marquez: None. K. Wennhold: None. A. Quaas: None. C. Bruns: None. C. Mauch: None. H. Löser: None. D. Stippel: None. H. Schlößer: None.

Download Full-text

Increased Risk of Cutaneous Squamous Cell Carcinoma in Organ Transplant Recipients and Patients on Chronic Dialysis: A Cancer Registry-based Study in Taiwan

Acta Dermato Venereologica ◽

10.2340/00015555-3350 ◽

2019 ◽

Vol 99 (13) ◽

pp. 1275-1281

Author(s):

C Tang ◽

Y Sue ◽

W Hsieh ◽

Y Wang ◽

C Wang

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Cancer Registry ◽

Squamous Cell ◽

Organ Transplant ◽

Cutaneous Squamous Cell Carcinoma ◽

Chronic Dialysis ◽

Transplant Recipients ◽

Organ Transplant Recipients ◽

Increased Risk

Download Full-text

Viral Enteritis in Solid-Organ Transplantation

Viruses ◽

10.3390/v13102019 ◽

2021 ◽

Vol 13 (10) ◽

pp. 2019

Author(s):

Anum Abbas ◽

Andrea J. Zimmer ◽

Diana Florescu

Keyword(s):

Solid Organ Transplantation ◽

Organ Transplant ◽

Solid Organ Transplant ◽

Solid Organ ◽

Transplant Recipients ◽

Post Transplantation ◽

Organ Transplant Recipients ◽

Increased Risk ◽

Viral Enteritis ◽

Solid Organ Transplant Recipients

Solid organ transplant recipients are at increased risk for infections due to chronic immunosuppression. Diarrhea is a commonly encountered problem post transplantation, with infectious causes of diarrhea being a frequent complication. Viral infections/enteritides in solid organ transplant recipients often result from frequently encountered pathogens in this population such as cytomegalovirus, adenovirus, and norovirus. However, several emerging viral pathogens are increasingly being recognized as more sensitive diagnostic techniques become available. Treatment is often limited to supportive care and reduction in immunosuppression, though antiviral therapies mayplay a role in the treatment in certain diseases. Viral enteritis is an important entity that contributes to morbidity and mortality in transplant recipients.

Download Full-text

Skin Cancers and Lung Transplant

Seminars in Respiratory and Critical Care Medicine ◽

10.1055/s-0041-1728798 ◽

2021 ◽

Vol 42 (03) ◽

pp. 483-496

Author(s):

Reason Wilken ◽

John Carucci ◽

Mary L. Stevenson

Keyword(s):

Cell Carcinoma ◽

Lung Transplant ◽

Radiation Treatment ◽

Organ Transplant ◽

Adjuvant Radiation ◽

Solid Organ ◽

Transplant Recipients ◽

Organ Transplant Recipients ◽

Skin Cancers ◽

Increased Risk

AbstractIt is well known that solid-organ transplant recipients (SOTRs) have a 65- to 100-fold increase in the risk of developing skin cancer, namely, nonmelanoma skin cancers (NMSCs) such as cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC). In addition, these patients are also at increased risk for development of melanoma as well as other less common cutaneous malignancies (Merkel's cell carcinoma, Kaposi's sarcoma). SOTRs with NMSC (namely cSCC) are also at significantly increased risk of poor clinical outcomes including local recurrence, nodal and distant metastasis, and disease-specific death relative to patients who are not immunosuppressed. Increased surveillance and monitoring in patients at risk of aggressive disease and poor outcomes who are on immunosuppression is essential in patients with lung transplants given the high degree of immunosuppression. Increased awareness of risks, treatments, and management allows for improved outcomes in these patients. This article will provide an overview of the risk factors for the development of cutaneous malignancies in organ transplant recipients as well as a detailed discussion of various immunosuppressant and prophylactic medications used in this patient population that contribute to the risk of developing cutaneous malignancies, with an emphasis on NMSC (cSCC and BCC) in lung transplant recipients. Finally, this article includes a discussion on the clinical and dermatologic management of this high-risk immunosuppressed population including a review of topical and systemic agents for field therapy of actinic damage and chemoprevention of keratinocyte carcinomas. In addition, indications for additional treatment and preventive measures such as adjuvant radiation treatment after surgical management of cutaneous malignancies and potential modification of immunosuppressive medication regimens are discussed.

Download Full-text

Risk of cancer following immunosuppression in organ transplant recipients and in HIV-positive individuals in southern Europe

European Journal of Cancer ◽

10.1016/j.ejca.2007.07.015 ◽

2007 ◽

Vol 43 (14) ◽

pp. 2117-2123 ◽

Cited By ~ 79

Author(s):

Diego Serraino ◽

Pierluca Piselli ◽

Ghil Busnach ◽

Patrizia Burra ◽

Franco Citterio ◽

...

Keyword(s):

Organ Transplant ◽

Hiv Positive ◽

Southern Europe ◽

Transplant Recipients ◽

Organ Transplant Recipients ◽

Risk Of Cancer

Download Full-text

The Role of Systems Vaccinology in Understanding the Immune Defects to Vaccination in Solid Organ Transplant Recipients

Frontiers in Immunology ◽

10.3389/fimmu.2020.582201 ◽

2020 ◽

Vol 11 ◽

Author(s):

Nicholas Scanlon ◽

Youssef Saklawi ◽

Nadine Rouphael

Keyword(s):

Systems Biology ◽

Organ Transplant ◽

Solid Organ Transplant ◽

Solid Organ ◽

Transplant Recipients ◽

Organ Transplant Recipients ◽

Organ Rejection ◽

Increased Risk ◽

Solid Organ Transplant Recipients ◽

Immune Defects

Solid organ transplant recipients (SOTRs) are at increased risk for many infections, whether viral, bacterial, or fungal, due to immunosuppressive therapy to prevent organ rejection. The same immune defects that render transplanted patients susceptible to infection dampen their immune response to vaccination. Therefore, it is vital to identify immune defects to vaccination in transplant recipients and methods to obviate them. These methods can include alternative vaccine composition, dosage, adjuvants, route of administration, timing, and re-vaccination strategies. Systems biology is a relatively new field of study, which utilizes high throughput means to better understand biological systems and predict outcomes. Systems biology approaches have been used to help obtain a global picture of immune responses to infections and vaccination (i.e. systems vaccinology), but little work has been done to use systems biology to improve vaccine efficacy in immunocompromised patients, particularly SOTRs, thus far. Systems vaccinology approaches may hold key insights to vaccination in this vulnerable population.

Download Full-text

Incidence and Treatment of Cancer in Transplant Recipients

Journal of Transplant Coordination ◽

10.1177/090591999800800209 ◽

1998 ◽

Vol 8 (2) ◽

pp. 105-112 ◽

Cited By ~ 1

Author(s):

Maureen P. Flattery

Keyword(s):

De Novo ◽

Solid Organ Transplantation ◽

Organ Transplant ◽

Cardiac Transplant ◽

Solid Organ ◽

Transplant Recipients ◽

Organ Transplant Recipients ◽

Organ Rejection ◽

Increased Risk ◽

Actuarial Risk

Solid organ transplantation has been an accepted mode of therapy for the treatment of end-stage organ diseases for many years. Recipients' survival, however, has been hindered by organ rejection and the comorbid diseases that develop as a result of immunosuppressive therapy. In particular, organ transplant recipients have an increased risk of developing cancer de novo after transplantation. Prevalence ranges from 4 to 18% with an average incidence of 6%. Data submitted to the Cincinnati transplant tumor registry have revealed that cancers prevalent in the general population exhibited no increase in rate and may even show a slight decline in the transplant population. Length of survival after transplantation is associated with the likelihood of having cancer; the longer the recipient survives, the greater the chance. The actuarial risk among 124 cardiac transplant recipients was 2.7+/-1.9% at 1 year and 25.6+/-11% at 5 years. This article will review the current literature on the incidence and treatment of cancer in solid organ transplant recipients.

Download Full-text