Blood Eosinophilia Is an on-Treatment Biomarker in Patients with Solid Tumors Undergoing Dendritic Cell Vaccination with Autologous Tumor-RNA

Abstract

Background: The approvals of immune checkpoint inhibitors for several cancer types and the rapidly growing recognition that T cell-based immunotherapy significantly improves outcomes for cancer patients led to a re-emergence of cancer vaccines, including dendritic cell (DC)-based immunotherapy. Blood and tissue biomarkers to identify responders and long-term survivors and to optimize cost and cost-effectiveness of treatment are greatly needed. We wanted to investigate whether blood eosinophilia is a predictive biomarker for patients with solid tumors receiving vaccinations with DCs loaded with autologous tumor-RNA. Methods: In total, 67 patients with metastatic solid tumors, who we treated with autologous monocyte-derived DCs transfected with total tumor mRNA, were serially analyzed for eosinophil counts and survival over the course of up to 14 years. Eosinophilic counts were performed on peripheral blood smears. Results: Up to 87% of the patients treated with DC-based immunotherapy experienced at least once an eosinophilia of ≥ 5% after initiation of therapy; 61 % reached levels of ≥ 10% eosinophils, and 13% of patients showed eosinophil counts of 20% or above. While prevaccination eosinophil levels were not associated with survival, patients with blood eosinophilia at any point after initiation of DC-based immunotherapy showed a trend towards longer survival. There was a statistically significant difference for the patients with eosinophil counts of 20% or more (p = 0.03). In those patients, survival was prolonged to a median of 58 months (range 2–111 months), compared to a median of 20 months (range 0–119 months) in patients with lower eosinophil counts. In 12% of the patients, an immediate increase in eosinophil count of at least 10 percentage points could be detected after the first vaccine, which also appeared to correlate with survival (65 vs. 24 months; p = 0.06). Conclusion: Blood eosinophilia appears to be an early, on-therapy biomarker in patients with solid tumors undergoing vaccination with RNA-transfected DC, specifically autologous tumor mRNA-transfected DC vaccines, and it correlates with long-term patient outcome. Eosinophilia should be systematically investigated in future trials.

Combining chemotherapy and autologous peptide‐pulsed dendritic cells provides survival benefit in stage IV melanoma patients

“…This observation, however, needs more investigation. Interestingly, the recent 12-years follow-up analysis of DC-vaccinated melanoma patients by the Erlangen group [11] could not corroborate some correlations that would have seemed obvious at first glance: Prolonged survival did not correlate with numbers of regulatory T cells or myeloid-derived suppressor cells (MDSC) cells, or with frequencies of vaccine-specific T cells (as determined by Elispot and tetramer staining) in the blood, but rather with strong reactions at the vaccine injection sites, and with blood eosinophilia of 20 % or more at any time point during (though not before) vaccination therapy [44]. Similarly, a substantial proportion (50 %) of our patients treated with DC-based immunotherapy plus chemotherapy experienced at least once an eosinophilia of 5 % or more during the course of therapy, but only one of 41 (2.4 %) reached levels of more than 10 %, and none had more than 20 %.…”

Immunity and Breast Cancer: Focus on Eosinophils

“…More recently, several studies have shown that eosinophils also play a role in the immune response in the presence of cancer. Several studies have been conducted to assess the role of eosinophils in both tumor tissue and circulating eosinophils [ 19 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 ]. In particular, circulating eosinophils have mainly been studied during immunotherapy in solid tumors [ 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 ].…”

“…Several studies have been conducted to assess the role of eosinophils in both tumor tissue and circulating eosinophils [ 19 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 ]. In particular, circulating eosinophils have mainly been studied during immunotherapy in solid tumors [ 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 ]. Less information is available regarding their role in patients treated with chemotherapy [ 72 , 73 ].…”

“…The role of the peripheral eosinophil count was widely studied in several cancer types, namely melanoma and lung cancer, during treatment with immunotherapy. In these patients, an association between both high baseline eosinophil count or increased count during treatment and better response to treatment or survival has been observed [ 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 ]. Their role in breast cancer is less known, with only a few reports studying the role of circulating eosinophils ( Table 2 ).…”

Kombination von Chemotherapie und autologen, Peptid‐beladenen dendritischen Zellen bringt Überlebensvorteil bei Melanompatienten im Stadium IV

“…Die detaillierte 12‐Jahre‐Follow‐up‐Untersuchung von DZ‐vakzinierten Melanompatienten der Erlanger Gruppe [11] ] konnte interessanterweise keine Korrelationen finden, die prima vista vermutet worden wären: Verlängertes Überleben korrelierte weder mit der Zahl der regulatorischen T‐Zellen noch mit der Frequenz der myeloiden Suppressorzellen (MDSC) und der Vakzine‐spezifischen T‐Lymphozyten im Blut (bestimmt mittels Elispot und Tetramer‐Methodik). Hingegen zeigte sich eine Korrelation mit starken Lokalreaktionen an der Injektionsstelle der Vakzine und mit einer Eosinophilie im Blut von 20 % oder mehr im Verlauf der Therapiedauer (jedoch nicht vor Therapiebeginn) [44]. In ähnlicher Weise konnte auch in der Hälfte unserer mit DZ plus Chemotherapie‐behandelten Patienten zumindest zu einem Zeitpunkt im Verlauf der Therapie eine Eosinophilie von 5 % oder mehr nachgewiesen werden.…”