Immunosuppression Modifications Based on an Immune Response Assay

Ravaioli, Matteo; Neri, Flavia; Lazzarotto, Tiziana; Bertuzzo, Valentina Rosa; Gioia, P. Di; Stacchini, Giacomo; Morelli, Cristina; Ercolani, Giorgio; Cescon, Matteo; Chiereghin, Angela; Gaudio, Massimo Del; Cucchetti, Alessandro; Pinna, Antonio

doi:10.1097/tp.0000000000000650

Cited by 79 publications

(70 citation statements)

References 36 publications

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“…In addition, simple and non-invasive immunomonitoring methods are required as markers for early stage cancer or tumor recurrence. Although several systems have been shown to strongly predict poor prognosis (19)(20)(21), personalized medicine requires the establishment of tumor-specific immunomonitoring systems for predicting tumor recurrence.…”

Section: Discussionmentioning

confidence: 99%

Peripheral Tr1 and Foxp3+ Treg as Markers of Recurrent Malignancies in Patients with Hepato-Biliary Pancreatic Cancers

Ikemoto

Shimada

Ishikawa

et al. 2017

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Abstract. Background Foxp3 + regulatory T cells (Foxp3 + Tregs) play an important role in tumor immunity (1-3). Populations of peripheral Foxp3 + Tregs were found to be greater in pancreatic cancer patients than in healthy controls, with peripheral Foxp3 + Treg populations strongly correlating with TMN classifications (4). In addition, peripheral Foxp3 + Treg populations were found to significantly correlate with the pathological aggressiveness of intraductal papillary mucinous neoplasms (IPMNs), a correlation dependent on Notch signaling (5). Although Treg populations have been reported to be higher in peritumoral lesions and in draining lymph nodes, the precise mechanism underlying the increase in peripheral Tregs in cancer patients has not been determined (6, 7).Treg expansion following organ transplantation has been reported to depend on indoleamine 2, 3-dioxygenase (IDO) activity of dendritic cells (DCs) (8). IDO is a critical enzyme for maintaining pregnancy (9) and plays an important role in tumor immunity (10,11). An investigation of the associations of IDO with IPMN aggressiveness and Treg immunity showed that Treg increases induced by IDO + DCs are associated with peritumoral lesions (12). However, the mechanism underlying the expansion of Tregs in peripheral blood, as well as in the peritumoral environment, remains unclear. Tregs are easily influenced by other factors that alter host immunology, such as infection and chemo/radiation therapy, suggesting the need for more precise and stable immunological parameters to evaluate tumor immunity, especially after surgery.CD4 + CD49b + LAG3 + regulatory T cells (type 1 regulatory T cells, or Tr1s) were recently reported to have strong regulatory activities in autoimmune diseases (13). Tr1s were originally found in the peripheral blood of patients with severe combined immunodeficiency and long-term mixed chimerism after human leukocyte antigen (HLA)-mismatched fetal liver hematopoietic stem cell transplantation (14). The primary 5541

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Section: Discussionmentioning

confidence: 99%

Peripheral Tr1 and Foxp3+ Treg as Markers of Recurrent Malignancies in Patients with Hepato-Biliary Pancreatic Cancers

Ikemoto

Shimada

Ishikawa

et al. 2017

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“…Survival outcomes after LT have constantly improved using upgraded immunosuppressive agents [165]. However, the inadequate or excessive immunosuppression is associated with a higher risk of rejection, higher incidence of infection, drug toxicity, and increased mortality [166][167][168][169][170]. Experimental studies in rats have investigated the effect of immunosuppressive agents on the intestinal microbiota in LT.…”

Section: Gut Microbiota and Hepatic Ischemia Reperfusion In Liver Surmentioning

confidence: 99%

Current Knowledge about the Effect of Nutritional Status, Supplemented Nutrition Diet, and Gut Microbiota on Hepatic Ischemia-Reperfusion and Regeneration in Liver Surgery

et al. 2020

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Ischemia-reperfusion (I/R) injury is an unresolved problem in liver resection and transplantation. The preexisting nutritional status related to the gut microbial profile might contribute to primary non-function after surgery. Clinical studies evaluating artificial nutrition in liver resection are limited. The optimal nutritional regimen to support regeneration has not yet been exactly defined. However, overnutrition and specific diet factors are crucial for the nonalcoholic or nonalcoholic steatohepatitis liver diseases. Gut-derived microbial products and the activation of innate immunity system and inflammatory response, leading to exacerbation of I/R injury or impaired regeneration after resection. This review summarizes the role of starvation, supplemented nutrition diet, nutritional status, and alterations in microbiota on hepatic I/R and regeneration. We discuss the most updated effects of nutritional interventions, their ability to alter microbiota, some of the controversies, and the suitability of these interventions as potential therapeutic strategies in hepatic resection and transplantation, overall highlighting the relevance of considering the extended criteria liver grafts in the translational liver surgery.

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“…The immunosuppression protocol was tacrolimus and tapering steroids in all patients, although additional immunosuppressants were permitted. The interventional arm had reduced trough concentration of tacrolimus, which resulted in less infections (42% vs. 54.9%; P < 0.05), with similar biopsy‐proven ACR rates (19% vs. 13.7%; P = NS), and improved survival rates at 12 months (95% vs. 82%; P < 0.01) . Although it seems that Immuknow adds some information to liver tests and trough concentrations of CNI, more studies are warranted to confirm these observations.…”

Section: Future Directionsmentioning

confidence: 89%

Biopsy-proven acute cellular rejection as an efficacy endpoint of randomized trials in liver transplantation: a systematic review and critical appraisal

et al. 2016

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Biopsy-proven acute cellular rejection (ACR) is the primary efficacy endpoint in most randomized trials evaluating immunosuppression in liver transplantation. However, ACR is not a major cause of graft loss, and a certain grade of immune activation may be even beneficial for long-term graft acceptance. Validated criteria to select candidates for liver biopsy are lacking, and routine clinical practice relies on liver tests, which are inaccurate markers of ACR. Indeed, both the agreement among clinicians to select candidates for liver biopsy and the correlation between the clinical suspicion of ACR and histological findings are poor. In randomized trials evaluating immunosuppression protocols, this concern grows exponentially due to the open-label and multicenter nature of most studies. Therefore, biopsy-proven ACR is a suboptimal efficacy endpoint given its limited impact on prognosis and the heterogeneous diagnosis, which may increase the risk of bias. Chronic rejection and/or graft loss would be more appropriate endpoints, but would certainly require larger studies with prolonged surveillances. An objective method to select candidates for liver biopsy is therefore urgently needed, and only severe episodes of histological ACR should be considered as potentially harmful. Emerging surrogate markers of ACR and antibody-mediated rejection require further investigation to determine their clinical role.

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Immunosuppression Modifications Based on an Immune Response Assay

Abstract: Immune function testing provided additional data which helped optimize immunosuppression and improve patient outcomes.

Cited by 79 publications

References 36 publications

Peripheral Tr1 and Foxp3+ Treg as Markers of Recurrent Malignancies in Patients with Hepato-Biliary Pancreatic Cancers

Peripheral Tr1 and Foxp3+ Treg as Markers of Recurrent Malignancies in Patients with Hepato-Biliary Pancreatic Cancers

Current Knowledge about the Effect of Nutritional Status, Supplemented Nutrition Diet, and Gut Microbiota on Hepatic Ischemia-Reperfusion and Regeneration in Liver Surgery

Biopsy-proven acute cellular rejection as an efficacy endpoint of randomized trials in liver transplantation: a systematic review and critical appraisal

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