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. 2024 Nov 19;25(22):12439.
doi: 10.3390/ijms252212439.

ICOSLG Is Associated with Anti-PD-1 and Concomitant Antihistamine Treatment Response in Advanced Melanoma

Domenico Mallardo  1 , Mario Fordellone  2 , Margaret Ottaviano  1 , Giuseppina Marano  1 , Maria Grazia Vitale  1 , Mario Mallardo  1 , Mariagrazia Capasso  1 , Teresa De Cristofaro  1 , Mariaelena Capone  1 , Teresa Meinardi  1 , Miriam Paone  1 , Patrizia Sabatelli  1 , Rosaria De Filippi  3 , Alessandra Cesano  4 , Ernesta Cavalcanti  5 , Corrado Caracò  6 , Sarah Warren  4 , Alfredo Budillon  7 , Ester Simeone  1 , Paolo Antonio Ascierto  1
Affiliations

ICOSLG Is Associated with Anti-PD-1 and Concomitant Antihistamine Treatment Response in Advanced Melanoma

Domenico Mallardo et al. Int J Mol Sci. .

Abstract

We previously demonstrated that patients with metastatic unresectable stage IIIb-IV melanoma receiving cetirizine (a second-generation H1 antagonist antihistamine) premedication with immunotherapy had better outcomes than those not receiving cetirizine. In this retrospective study, we searched for a gene signature potentially predictive of the response to the addition of cetirizine to checkpoint inhibition (nivolumab or pembrolizumab with or without previous ipilimumab). Transcriptomic analysis showed that inducible T cell costimulator ligand (ICOSLG) expression directly correlated with the disease control rate (DCR) when detected with a loading value > 0.3. A multivariable logistic regression model showed a positive association between the DCR and ICOSLG expression for progression-free survival and overall survival. ICOSLG expression was associated with CD64, a specific marker of M1 macrophages, at baseline in the patient samples who received cetirizine concomitantly with checkpoint inhibitors, but this association was not present in subjects who had not received cetirizine. In conclusion, our results show that the clinical advantage of concomitant treatment with cetirizine during checkpoint inhibition in patients with malignant melanoma is associated with high ICOSLG expression, which could predict the response to immune checkpoint inhibitor blockade.

Keywords: biomarker; cetirizine; checkpoint inhibition; cutaneous melanoma.

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Conflict of interest statement

Alessandra Cesano and Sarah Warren were employed at ESSA Pharma. The authors declare that this research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Gene signature expression in responder and non-responder patients (Wilcoxon test, p = 8.3 × 10−8). The signature included 15 genes, namely TRAF1, S100A9, S100A8, S100A12, OLR1, NF1, MMP9, LDHA, ITGAM, ICOSLG, HLA-DPA1, FSTL3, CST2, CLEC5A, and ANLN.
Figure 2
Figure 2
PFS according to having received or not received cetirizine in (A) patients with low ICOSLG expression (n = 30) and (B) patients with high ICOSLG expression (N = 86).
Figure 2
Figure 2
PFS according to having received or not received cetirizine in (A) patients with low ICOSLG expression (n = 30) and (B) patients with high ICOSLG expression (N = 86).
Figure 3
Figure 3
OS in patients treated or not treated with cetirizine and (A) with low ICOSLG expression (n = 30) or (B) with high ICOSLG expression (N = 86).
Figure 3
Figure 3
OS in patients treated or not treated with cetirizine and (A) with low ICOSLG expression (n = 30) or (B) with high ICOSLG expression (N = 86).
Figure 4
Figure 4
Multivariable survival analysis according to PFS (A) and OS (B) for ICOSLG expression. * p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001.
Figure 4
Figure 4
Multivariable survival analysis according to PFS (A) and OS (B) for ICOSLG expression. * p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001.
See this image and copyright information in PMC

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