The use of micronutrients such as vitamin D could improve the response to viral vaccines, particularly in immunosuppressed and immunosenescent subjects. Here, we analysed the association between serum 25-hydroxyvitamin D (25OHD) levels and the immune response elicited by the BNT162b2 vaccine in a cohort of 101 healthcare workers naïve for SARS-CoV-2 infection. We observed no significant differences in anti-spike (S) IgG and T-cell responses according to the 25OHD status at baseline. However, significant correlations between the 25OHD concentration at baseline and (i) the anti-S response (p < 0.020) and (ii) the neutralizing antibody (NT) titre (p = 0.040) at six months after the second dose were detected. We concluded that adequate levels of vitamin D may improve the immune response to mRNA vaccines such as BNT162b2, and that further larger studies are warranted in order to confirm these preliminary observations.

We present a series of twelve patients, bearing a wide range of solid malignancies, who received either PD-L1 or a combination of PD-L1 and CTLA-4 inhibitors. Following immunotherapy administration, they exhibited the clinical signs indicative of renal toxicity, including increased serum creatinine levels, proteinuria, nephrotic syndrome and/or hematuria. All patients underwent renal biopsy. Results: All cases demonstrated some degree of interstitial inflammation and tubular injury, while in five patients, glomerular alterations consistent with a specific glomerulopathy were also observed: secondary “lupus-like” membranous glomerulopathy in two cases and membranoproliferative glomerulonephritis, IgA glomerulonephritis and secondary AA amyloidosis in each of the remaining three patients. The two patients with “lupus-like” nephritis and the one with amyloidosis experienced nephrotic syndrome, while their creatinine was within normal range. In the remaining nine cases, deterioration of renal function was the main manifestation. Conclusion: Our findings harmonize with bibliographical data that identify tubulointerstitial nephritis as the most frequent histological lesion related to ICIs administration. The preferential involvement of tubulointerstitial tissue could be associated with the reported higher expression levels of PD-L1 on tubular epithelial cells, compared to glomeruli. On the other hand, glomerular involvement is probably a consequence of a systemic immune system reconstruction, induced by immune-checkpoints inhibition.

Introduction: New Immuno- Checkpoint inhibitors (ICIs) functioning as PD-1- PDL-1 blockers are nowadays used in a majority of anticancer treatments. Many immune- related Adverse Events (irAEs) are published daily; severe skin toxicities, Stevens Johnson/ Toxic Epidermal Necrolysis (SJS/TEN) are seldom reported. Case report: Herein, we present two interesting skin sever toxicity cases of lung cancer patients, undergoing PD-1- PDL-1 Immunotherapy. In both cases, a morbilliform rash with documented histological Toxic Epidermal Necrolysis Pattern /Stevens Johnson findings, was thoroughly studied. Management & Outcome: Both cases were therapeutically managed according to guidelines with different outcome. Discussion: Two focused cases of irAEs, is the rationale, to briefly review mechanisms of major toxicities caused by PD-1/PD-L1 blockade, and present all new data in their precise management. ICIs’ association with SJS/ TEN still remains unclear; underlying urgent need for further studies. It is important to alert physicians to promptly identify life threatening irAEs. Being familiar, provides management efficacy, safe resolve and encourage beneficial balanced cost effective treatments.

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