In a living organism, cancer cells function in a specific microenvironment, where they exchange numerous physical and biochemical cues with other cells and the surrounding extracellular matrix (ECM). Immune evasion is a clinically relevant phenomenon, in which cancer cells are able to direct this interchange of signals against the immune effector cells and to generate an immunosuppressive environment favoring their own survival. A proper understanding of this phenomenon is substantial for generating more successful anticancer therapies. However, classical cell culture systems are unable to sufficiently recapture the dynamic nature and complexity of the tumor microenvironment (TME) to be of satisfactory use for comprehensive studies on mechanisms of tumor immune evasion. In turn, 3D-bioprinting is a rapidly evolving manufacture technique, in which it is possible to generate finely detailed structures comprised of multiple cell types and biomaterials serving as ECM-analogues. In this review, we focus on currently used 3D-bioprinting techniques, their applications in the TME research, and potential uses of 3D-bioprinting in modeling of tumor immune evasion and response to immunotherapies.

Post-transplantation lymphoproliferative disorder (PTLD) is a life-threatening complication of solid organ transplantation (SOT). Its development risk varies among organ graft recipients. In this study, retrospective data were analyzed to compare PTLD’s risk and prognostic factors between adult kidney and liver transplant recipients (KTRs and LTRs, respectively). Over 15 years, 2598 KTRs and 1378 LTRs were under observation at our center. Sixteen KTRs (0.62%) and twenty-three LTRs (1.67%) were diagnosed with PTLD. PTLD developed earlier in LTRs (p < 0.001), SOT patients > 45 years old (p = 0.002), and patients receiving tacrolimus (p < 0.001) or not receiving cyclosporin (p = 0.03) at diagnosis. Tacrolimus use, male sex, and age > 45 years old significantly affected the time of PTLD onset in KTRs (hazard ratio (HR) = 18.6, 7.9 and 5.2, respectively). Survival was longer in LTRs < 45 years old (p < 0.009). LTRs were more likely than KTRs to achieve complete remission (p = 0.039). Factors affecting PTLD development and outcome differ between KTRs and LTRs; thus, these populations should be separately evaluated in future studies.

Background and Aims Solid organ transplantation (SOT) has become the therapy of choice for the treatment of end-stage organ failure. The non-steroidal anti-inflammatory drugs (NSAIDs) and over-the- counter (OTC) painkillers are ofenly used. In a group of SOT recipients, co-morbidities and immunosuppression interactions significantly increase the risk of side effects. The aim of the study was to analyze the frequency and reasons of the NSAIDs and/or painkillers use by renal (RTRs) and heart transplant recipients (HTRs). Method This cross-sectional study was perfomed in randomly selected 388 RTRs and 286 HTRs aged from 18 to 82 years. The original annonymus questionnaire consisting of 32 questions related to health status and NSAIDs and/or analgesics use was applied. Questionnaire was distributed in paper-form and completed with the participation of medical worker either in transplant cardiosurgical or renal transplantation center. “R” v. 3.6.1. was used for statistical analysis and p-value &lt;0.05 was considered significant. Results 674 patients were surveyed. All patients: 34,3% (n=231) women and 65,7% (n=443) men in the mean age of 62.27 years completed the questionnaire. 70% (n=451) of respondents declared using NSAIDs and/or analgesics. Furthermore, 87% of participants declared using OTC painkillers. The most frequent causes for using analgesics are listed in Table 1. 68,5% of our SOT recipients declared that they were informed by their doctor about consequences of other drugs used with immunosuppression. 69,9% of HTRs comparing to 54,3% of RTRs ask their doctor before taking analgesics. Nevertheless, the survey also showed that every third patient (31,5%) was not sufficiently informed. Acetaminophen was the first-choice drug taken by 67,6% of patients (Fig. 1). Only 20% of patients declared not using NSAIDs and/or analgesics at all. Conclusion The result of our study indicates high frequency of NSAID and painkillers usage by RTRs and HTRs. Considering potentially harmful influence on transplanted organs, the costs of transplantation and post-trasplant care, the awareness of drug- related side effects or interactions and patients compliance need to be highlighted.

Background and Aims Post-transplantation lymphoprolipherative disorder [PTLD] is a serious, potentially fatal complication of transplantation [Tx], pathogenesis of which remains to be fully understood. Due to the intrinsic difficulty of assembling a large cohort of rare disease patients, most research papers have investigated PTLD in the general graft recipient population. They report however, that the relative risk of disease development significantly varies in relation to the type of transplanted organ, with multiorgan and intestinal graft recipients possessing the highest risk (RR=239.5), liver (RR=29.9) and the lowest for kidney transplant recipients (RR=12.6). The aim of this study was to investigate the factors contributing to the development, course, treatment and outcomes of PTLD and compare their impact on the populations of liver [LTR] and kidney [KTR] transplant recipients. Method In this retrospective cohort study we have included all KTRs and LTRs diagnosed with PTLD at our centres between 2002 and 2017. The following data were collected from the patients’ medical records: immunosuppression (IS), viral infections, PTLD type, treatment and outcomes. Mann-Whitney U-test was used to assess the differences in group composition, and the Log-rank test was used to compare Kaplan-Meier curves. Statistical analysis was performed in R version 3.2.3., p-values below .05 were considered statistically significant. Results We have identified 23 LTR and 16 KTR who matched our inclusion criteria. The mean age was 40.69 years. 61.5% of the patients were male, 38.5% female. Analysis of Kaplan-Meier curves revealed that PTLD occurred earlier in: LTRs (p&lt;.001); patients above the median age of 45 years at Tx (p=.002); patients whose IS regimens at the time of PTLD diagnosis contained tacrolimus [TAC] (p&lt;.001) or did not contain cyclosporin [CsA]. Among KTRs PTLD was diagnosed earlier in males (p&lt;0.05), patients over 45 years at Tx (p&lt;0.05), and those receiving TAC-containing IS regimens at PTLD diagnosis (p&lt;0.05). These factors were not statistically significant for LTRs, among whom PTLD development was affected by the presence of MMF in IS regimens at diagnosis (p&lt;0.05). Survival time was longer for patients receiving MMF-containing IS regimens (p&lt;0.05). LTRs were more likely than KTRs to achieve complete remission in response to treatment (p&lt;0.05). Conclusion Our results indicate, that in comparable KTR and LTR populations, the course of PLTD and response to treatment vary significantly. Factors such as patients’ age at transplantation, sex, type of maintenance IS have a different impact depending on graft type. In our opinion these findings, when applied to further research, could enhance our ability to identify patients at risk and potentially lead to the formation of more personalised guidelines to the diagnosis and treatment of PTLD.