Despite advances in their diagnosis and treatment, pediatric cancers remain among the leading causes of death in childhood. The development of immunotherapies and other forms of targeted therapies has significantly changed the prognosis of some previously incurable cancers in the adult population. However, so far, the results in pediatric cohorts are disappointing, which is mainly due to differences in tumor biology, including extreme heterogeneity and a generally low tumor mutational burden. A central role in the limited efficacy of immunotherapeutic approaches is played by the peculiar characteristics of the tumor microenvironment (TME) in pediatric cancer, with the scarcity of tumor infiltration by T cells and the abundance of stromal cells endowed with lymphocyte suppressor and tumor-growth-promoting activity. Thus, progress in the treatment of pediatric solid tumors will likely be influenced by the ability to modify the TME while delivering novel, more effective therapeutic agents. In this review, we will describe the TME composition in pediatric solid tumors and illustrate recent advances in treatment for the modulation of immune cells belonging to the TME.

Background: A paediatric cancer diagnosis is a profound stressor for the entire family system. Although coping strategies are well-studied, their link to the quality of the parent–child attachment relationship remains less explored. In this study, we investigated whether dyadic attachment dynamics—specifically closeness and conflict between parent and child—are associated with the use of adaptive or maladaptive coping strategies in caregivers of children undergoing active treatment for oncohaematological diseases. Methods: We conducted a multicentre, cross-sectional study across three Italian paediatric oncohaematology centres. A total of 165 caregivers of 91 paediatric patients aged 3–17 years completed self-report measures assessing parent–child relationship quality (Child–Parent Relationship Scale-CPRS), coping strategies (COPE-NVI), perceived social support (MSPSS), and resilience (RS-14). We tested whether the quality of the parent–child attachment relationship is associated with caregivers’ coping strategies. We hypothesised that Attachment Closeness would be associated with adaptive coping (Positive Attitude, Social Support, Problem Orientation), whereas Attachment Conflict would be associated with maladaptive coping (Avoidance). We conducted multiple linear regression models, adjusted for key covariates and with robust standard errors clustered at the family level, to test these hypotheses. Results: Higher levels of emotional closeness (CPRS) were significantly associated with greater use of adaptive coping strategies, specifically Positive Attitude (β = 0.20, p = 0.049) and Problem Orientation (β = 0.26, p = 0.002), even after controlling for sociodemographic factors, social support, and resilience. Conversely, higher levels of relational conflict were significantly associated with greater use of the maladaptive Avoidance strategy (β = 0.14, p = 0.015). The hypothesis linking closeness to Social Support seeking was not supported. Conclusions: The findings suggest that the parent–child attachment relationship is a significant correlate of caregiver coping strategies in caregivers of children with cancer. Interventions aimed at supporting the caregiver–child dyad by fostering emotional closeness and reducing conflict may promote more adaptive parental coping mechanisms, thereby enhancing family resilience and psychological adjustment throughout the treatment journey.

Polyomavirus BK (BKPyV)-associated nephropathy (BKPyV-nephropathy) remains a significant cause of premature kidney allograft failure. In the absence of effective antiviral treatments, current therapeutic approaches rely on immunosuppression (IS) reduction, possibly at the risk of inducing alloimmunity. Therefore, we sought to explore the long-term effects of a tailored viro-immunologic surveillance and treatment program for BKPyV on the development of alloimmunity and kidney graft outcome. Forty-five pediatric kidney transplant recipients were longitudinally monitored for BKPyV replication, virus-specific immunity, and donor-specific HLA antibodies (DSAs). DNAemia developed in 15 patients who were treated with stepwise IS reduction. Among the other 30 patients, 17 developed DNAuria without DNAemia and 13 always resulted as BKPyV-negative. All patients with DNAemia cleared BKPyV after having mounted a virus-specific cellular immune response, and no biopsy-proven BKPyV-nephropathy was observed. The presence of cytotoxic populations directed to the BKPyV Large-T (LT) antigen early after transplantation protected kidney recipients from developing BKPyV replication, and the appearance of LT-specific T cells in viruric patients prevented the development of BKPyV-DNAemia. In our cohort, no significant correlation was observed between BKPyV-DNAemia and the development of DSA and antibody-mediated rejection. However, patients who experienced and cleared BKPyV-DNAemia had a worse allograft survival at a median follow-up of 18.9 years (p = 0.048). These data need to be confirmed in larger cohorts.

Background: A paediatric cancer diagnosis is a profound stressor for the entire family system. While coping strategies are well-studied, their link to the quality of the parent-child attachment relationship remains less explored. This study investigates whether dyadic attachment dynamics — specifically closeness and conflict between parent and child — are associated with the use of adaptive or maladaptive coping strategies in caregivers of children undergoing active treatment for oncohaematological diseases. Methods: A multicentre, cross-sectional study was conducted across three Italian paediatric oncohaematology centres. A total of 165 caregivers of 91 paediatric patients completed self-report measures assessing parent-child relationship quality (Child-Parent Relationship Scale - CPRS), coping strategies (COPE-NVI), perceived social support (MSPSS), and resilience (RS-14). The study aimed to test whether the quality of the parent–child attachment relationship is associated with caregivers’ coping strategies. We hypothesised that Attachment Closeness would be associated with adaptive coping (Positive Attitude, Social Support, Problem Orientation), whereas Attachment Conflict would be associated with maladaptive coping (Avoidance). Hierarchical multiple linear regressions, adjusted for key covariates and clustered by centre, were conducted to test these hypotheses. Results: Higher levels of emotional closeness (CPRS) were significantly associated with greater use of adaptive coping strategies, specifically Positive Attitude (β = 0.20, p = 0.049) and Problem Orientation (β = 0.26, p = 0.002), even after controlling for sociodemographic factors, social support, and resilience. Conversely, higher levels of relational conflict were significantly associated with greater use of the maladaptive Avoidance strategy (β = 0.14, p = 0.015). The hypothesis linking closeness to Social Support seeking was not supported. Conclusions: The quality of the parent-child attachment is significantly and independently associated with coping styles in caregivers of children with cancer. Interventions aimed at supporting the caregiver–child dyad by fostering emotional closeness and reducing conflict may promote more adaptive parental coping mechanisms, thereby enhancing family resilience and psychological adjustment throughout the treatment journey.