Background: Tumor microenvironment (TME) can influence antitumor immunity and survival in Hodgkin lymphoma (HL) as previously published. However, most of this data has sparse clinical applicability. Flow cytometry (FC) has limited utility in HL diagnosis but its potential to assess TME has not been fully explored yet.
Aims: To determine the prognostic impact on survival of the percentage (%) of tumor infiltrating lymphocytes (TIL) and CD4/CD8 ratio in lymph nodes (LN) measured by FC.
Methods: We selected patients (pts) with HL, available LN FC data at diagnosis and i-PET scan, treated at our center from 2012-2020. FC was performed with 8-color panels according to Euroflow protocols. TIL % and CD4/CD8 ratio in LN by FC were compared to normal values reported (Battaglia, Immunology 2003) and stratified as low, normal and high. Response was assessed per Lugano recommendations. Progression free survival (PFS) was estimated with Kaplan-Meier, multivariate analysis with Cox regression, and variables were compared with log-rank test.
Results: 46 pts were included. Median age: 34 years. 24/27 with early stage had unfavorable risk and 11/19 with advanced disease had IPS≥3. 95% received ABVD. Complete response rate was 91.3%. 2 pts died. Median PFS: not reached (NR), 75th percentile 43 months (m), and median follow up: 49 m. i-PET negative (neg) pts had significantly better PFS (median NR vs 13.7 m in i-PET positive subgroup, p:0.014). Low LN TIL % was associated with inferior PFS (median 24.4 m vs. NR in pts with normal or high TIL, p:0.024). Regarding CD4/CD8 ratio, PFS rates were 100%, 75% and 60% in normal, low and high subgroups respectively, p:0.041. Both low TIL and positive i-PET remained independent predictors of survival on multivariate analysis with HR of 11.8 (CI 95% 1.9-72.7, p:0.021), and 7.7 (CI 95% 1.6-36.4, p:0.01) respectively. LN TIL % could further stratify outcomes in pts with neg i-PET scans. In this subset, pts with low TIL had a median PFS of 24.4 m and PFS rates of 33.3% vs. median NR in normal and high subgroups and PFS rates of 88.9 and 87.5% respectively, p:0.006.
Conclusions: LN TIL % measured by FC showed prognostic impact in our cohort of HL pts. Pts with low TIL had inferior PFS, even in those with optimal interim response where the median was only 2 years. This finding denotes the critical role of T cells to achieve cure. Checkpoint blockade might constitute an appealing approach in these pts to restore effective antitumor immunity.