Cellular and humoral immunity are both required for SARS-CoV-2 infection recovery and vaccine efficacy. The factors affecting mRNA vaccination-induced immune responses, in healthy and fragile subjects, are still under investigation. Thus, we monitored the vaccine-induced cellular and humoral immunity in healthy subjects and cancer patients after vaccination to define whether a different antibody titer reflected similar rates of cellular immune responses and if cancer has an impact on vaccination efficacy. We found that higher titers of antibodies were associated with a higher probability of positive cellular immunity and that this greater immune response was correlated with an increased number of vaccination side effects. Moreover, active T-cell immunity after vaccination was associated with reduced antibody decay. The vaccine-induced cellular immunity appeared more likely in healthy subjects rather than in cancer patients. Lastly, after boosting, we observed a cellular immune conversion in 20% of subjects, and a strong correlation between pre- and post-boosting IFN-γ levels, while antibody levels did not display a similar association. Finally, our data suggested that integrating humoral and cellular immune responses could allow the identification of SARS-CoV-2 vaccine responders and that T-cell responses seem more stable over time compared to antibodies, especially in cancer patients.

Trastuzumab deruxtecan (T-DXd) has demonstrated efficacy in HER2-positive and HER2-low breast cancer. Its main safety concern is interstitial lung disease, while clinically relevant hepatotoxicity is rarely reported. In our case report we describe a 49-year-old woman with HER2-positive advanced breast cancer that developed persistent grade 3 transaminase elevations after 2 cycles of T-DXd, refractory to corticosteroid treatment and requiring treatment discontinuation. This case underlines the unpredictable and idiosyncratic nature of T-DXd associated hepatotoxicity and the importance of liver function monitoring. Clinicians should consider DILI in patients with unexplained liver enzyme elevations during therapy. Further studies are needed to clarify mechanisms and risk factors.

Immune checkpoint inhibitors (ICIs) have transformed the treatment of several malignancies, but their efficacy and gastrointestinal (GI) immune-related adverse events (irAEs) vary considerably among patients. Growing evidence suggests that the gut microbiota and intestinal barrier integrity are associated with both therapeutic response and toxicity, although their causal contribution and clinical utility remain incompletely defined. Dysbiosis may disrupt epithelial homeostasis, increase intestinal permeability, and promote mucosal immune activation, potentially influencing antitumor immunity and susceptibility to ICI-induced colitis. Current biomarkers of intestinal permeability are limited by their indirect nature, lack of standardization, or poor spatial resolution. Probe-based confocal laser endomicroscopy (pCLE) enables real-time, in vivo visualization of epithelial abnormalities associated with barrier dysfunction, including fluorescein leakage, epithelial gaps, and cell shedding. In parallel, dietary and microbiota-directed interventions are being investigated as potential strategies to modulate intestinal homeostasis during ICI therapy, although evidence supporting their routine clinical use remains limited. This review summarizes current evidence linking the gut microbiota, intestinal barrier dysfunction, and cancer immunotherapy and discusses the potential role of pCLE as a candidate functional imaging tool in ICI-treated patients. We highlight current knowledge gaps and propose a translational framework integrating pCLE with microbiome profiling, circulating biomarkers, histopathology, and clinical outcomes to determine whether this approach can improve patient stratification and the early identification and monitoring of GI toxicity.

Immune checkpoint inhibitors (ICIs) have transformed the treatment of several malignancies, but their efficacy and gastrointestinal (GI) immune-related adverse events (irAEs) vary considerably among patients. Growing evidence suggests that the gut microbiota and intestinal barrier integrity are associated with both therapeutic response and toxicity, although their causal contribution and clinical utility remain incompletely defined. Dysbiosis may disrupt epithelial homeostasis, increase intestinal permeability, and promote mucosal immune activation, potentially influencing antitumor immunity and susceptibility to ICI-induced colitis. Current biomarkers of intestinal permeability are limited by their indirect nature, lack of standardization, or poor spatial resolution. Probe-based confocal laser endomicroscopy (pCLE) enables real-time, in vivo visualization of epithelial abnormalities associated with barrier dysfunction, including fluorescein leakage, epithelial gaps, and cell shedding. In parallel, dietary and microbiota-directed interventions are being investigated as potential strategies to modulate intestinal homeostasis during ICI therapy, although evidence for their clinical benefit and effects on intestinal barrier integrity remains limited. This review summarizes current evidence linking the gut microbiota, intestinal barrier dysfunction, and cancer immunotherapy and discusses the potential role of pCLE as a candidate functional imaging tool in ICI-treated patients. We highlight current knowledge gaps and propose a translational framework integrating pCLE with microbiome profiling, circulating biomarkers, histopathology, and clinical outcomes to determine whether this approach can improve patient stratification and the early identification and monitoring of GI toxicity.