906P - Multi-parameter flow cytometry analysis of circulating immune cell populations in recurrent/metastatic adenoid cystic carcinoma

Background

Adenoid cystic carcinoma (ACC) is characterized by high recurrence rates despite surgery and radiotherapy, and anti-PD-1/PD-L1 therapy has limited clinical efficacy in the recurrent/metastatic setting. This study sought to characterise circulating immune cell sub-sets and identify candidate targets for novel immunotherapies in ACC.

Methods

Blood samples from 22 anti-PD1/PDL1 naive ACC patients, 26 anti-PD1/PDL1 naive head and neck squamous cell carcinoma (SCC) patients and 13 healthy volunteers underwent multi-parameter flow cytometry for comprehensive classification of the immune cell populations, using commercially available validated panels. Results were analysed using FlowJo.

Results

This study identified significant expansion of CD14hi/CD16+ monocytes compared with healthy volunteers in a sub-population of ACC patients (mean 28%, range 10% to 58%, versus 9% range 1% to 20% p<0.05). This monocyte sub-set was also seen in the comparator group of SCC patients (mean 36%, range 12%-78%.) Expression levels of PDL1 on CD14+ monocytes was greater in ACC monocytes compared to samples from our SCC patient cohort (mean 60% v 32%; p=0.09). Furthermore, 55% of ACC patients had elevated COX-2 expression (greater than 30%), by intracellular fluorescence activated cell sorting in CD14+ monocytes compared with 22% in our SCC group. With regards to T cells, peripheral blood from ACC patients had a decreased CD4+/CD8+ ratio compared to SCC (2.85 vs 5.5.) Furthermore, a significantly higher proportion of CD8+ cells were naïve as defined by CCR7+/CD45RA+ (Mean 38% vs 16% p<0.01). No differences were observed in the proportions of NK T cells, though we did identify a highly significant reduction of TIGIT on them in ACC compared with SCC patients (16% versus 40% of total CD3+ p=<0.001).

Conclusions

This study provides insights into distinct immune cell subsets in ACC patients. Our findings suggest that novel immunotherapies, including targeting of COX-2, may be have a rationale in ACC. Additionally, TIGIT is associated with exhaustion and so the reduced expression of TIGIT on NK-T cells in ACC may help guide future trial selection.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The Christie NHS Foundation Trust.

Funding

Syncona.

Disclosure

K.J. Harrington: Financial Interests, Institutional, Advisory Board: Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Merck, MSD, Pfizer, Replimune, Oncolys, Vyriad, Idera; Financial Interests, Institutional, Other, Honoraria for lectures: Amgen, AstraZeneca, BMS, Boehringer Ingelheim; Financial Interests, Institutional, Advisory Board, Advisory board for CD47 assets: Arch Oncology; Financial Interests, Institutional, Advisory Board, Development of DDR assets: ARTIOS; Financial Interests, Institutional, Advisory Board, Development of exosomal STING agonist: Codiak; Financial Interests, Institutional, Advisory Board, Development of oncolytic adenovirus: PsiVac; Financial Interests, Institutional, Funding, Research: AstraZeneca, Boehringer Ingelheim, MSD; Financial Interests, Institutional, Funding, Development of oncolytic HSV platform.: Replimune; Non-Financial Interests, Leadership Role, Chair of Steering Committee: ART NET; Non-Financial Interests, Other, Member of Global Steering Committee: MR - Linac. R. Metcalf: Financial Interests, Personal, Advisory Board: Ayala, Bayer, Aptus Clinical, PCI Biotech, Oxsonics, Roche, Achilles Therapeutics; Financial Interests, Personal, Other, Honoraria: BMS, MSD, Sanofi. All other authors have declared no conflicts of interest.