Background: TIGIT (T-cell immunoreceptor with Ig and ITIM domains) is an inhibitory immune checkpoint receptor involved in tumor immune escape and T-cell exhaustion. Its main ligand, CD155, can be expressed by tumor cells and may contribute to suppression of the anti-tumor immune response through activation of the TIGIT/CD155 axis. In classical Hodgkin lymphoma (cHL), the biological and prognostic significance of this pathway remains poorly defined. We retrospectively evaluated TIGIT expression by immunohistochemistry and its association with clinical characteristics, survival outcomes, and CD155 expression on Reed–Sternberg cells.
Methods: Eighty-six patients with cHL were retrospectively analyzed. TIGIT expression was assessed on diagnostic biopsy specimens by immunohistochemistry and dichotomized as negative (score 0) or positive (scores 1–3). Clinical data regarding treatment response and outcome were available for 66 patients, who constituted the cohort for clinicopathological and outcome analyses. Patients were additionally stratified according to age (<40 vs ≥40 years). Overall survival (OS) was defined as the time from diagnosis to death from any cause or last follow-up, while event-free survival (EFS) was defined as the time from diagnosis to relapse, progression, or death. Survival curves were estimated using the Kaplan–Meier method and compared using the log-rank test. Due to incomplete information regarding the timing of relapse or progression, survival analyses were evaluable in 62 patients. In a subset of 10 patients, CD155 expression on Reed–Sternberg cells was also evaluated.
Results: Among the 86 patients evaluated for TIGIT expression, 42 (48%) were TIGIT-positive and 44 (52%) were TIGIT-negative. Among the 66 patients with available clinical follow-up data, 35 (53%) were TIGIT-positive and 31 (47%) were TIGIT-negative. Survival analysis was evaluable in 62 patients. With a median follow-up of 5.97 years, 7 deaths and 19 EFS events were observed. TIGIT expression was not significantly associated with stage, bulky disease, relapse, progression, or death. Likewise, no significant differences were observed in OS (log-rank p = 0.419) or EFS (log-rank p = 0.292) according to TIGIT status. Patients aged ≥40 years accounted for 42 of the 66 cases, whereas 24 were younger than 40 years. TIGIT positivity was more frequently observed in older patients (61.9% vs 37.5%, p = 0.075), who also showed a higher prevalence of advanced-stage disease (61.9%
Ombretta Annibali, Teresa Marafioti, Valeria Tomarchio, Adheesh Ghosh, Lara Antonelli, Muntasser Alsharabati, Salvatore Iachino, Harriet Hunter, Giulia Santoro, Sugerdana Padmasri, Antonella Bianchi, Simona Spreafico, Anna Crescenzi, Luigi Rigacci