Abstract 2810: Exploring T cell- repertoire in the tumor microenvironment during check-point inhibition in patients with metastatic solid tumors
Authors: Vinicius Araujo Barbosa de Lima, Morten Hansen, Kristoffer Staal Rohrberg, Iben Spangaard, Inge Marie Svane, Ulrik Lassen
Journal: Cancer Research (2019)

Abstract Background: Immunomodulation has improved anti-tumor activity. However, this treatment modality is only effective in a proportion of patients. Hence, analyzing changes in the tumor microenvironment is essential for understanding the variety of response patterns seen among patients undergoing the treatment. It also provides clinicians with valuable knowledge of possible new therapeutic targets. Aim: Assessment of the repertoire of T-cells (tumor-infiltrating lymphocytes -TIL) in the tumor microenvironment during check-point inhibition in patients with metastatic solid tumors. Material and methods: 35 patients with different metastatic solid tumors were included in the study at our Unit for Experimental Treatment at Rigshospitalet, Denmark. Patients were given treatment with check-point inhibitors targeting PD-1/PD-L1/CTLA-4 either in monotherapy or combined with other agents. Fresh tumor biopsies were taken at two time-points, namely, at baseline and on-treatment (50 days interval). T-cells were expanded in vitro with high doses of IL2 (6,000IU/mL IL2), harvested and cryopreserved for later use. Samples were analyzed using a multicolor flow cytometry panel. Response to the treatment was assessed radiologically using to RECIST criteria 1.1 and patients were divided in responder and non-responders. Results: Expansion was successful in seventeen patients and five other follow-up samples are still in culture at the moment. The current data analysis was run based on the seventeen cryopreserved samples. Among responders, we observed that baseline samples showed a statistically significant high percentage of effector CD8+(CD45RO+CCR7-) and CD8+naïve T cells(CD62L+), with p value 0.034 and 0.009, respectively. The presence of a high proportion of naïve CD8+Tcells in tumor microenvironment of responders could be explained by the fact that there is a high proportion of T cells surviving and becoming memory T cells and eventually effector T cells. No statistical difference was seen at the baseline expression of PD-1, either in the CD8 (p 0.66) or in the CD4 compartment (p 0.88). For follow-up samples, CD4+ effector memory T cells seemed to be more present among responders (p 0.009). Interestingly, NK-cells expressing CD56 (p 0.046) and co-expressing CD137 (p 0.005), known as an activation marker, appeared to be more present in samples from the responder group. CD4+T cells deriving form follow-up samples were also co-stained for LAG-3 revealing that responders had a low percentage of TILs expressing both markers (p 0.016). Paired-sample test will be run as the expansion phase for the remaining 5 samples still in culture is over. Conclusion: The preliminary findings of our study suggest that response achieved during check-point inhibition is reliant on the subset of T cells present in the tumor microenvironment and on how its composition changes over time. Citation Format: Vinicius Araujo Barbosa de Lima, Morten Hansen, Kristoffer Staal Rohrberg, Iben Spangaard, Inge Marie Svane, Ulrik Lassen. Exploring T cell- repertoire in the tumor microenvironment during check-point inhibition in patients with metastatic solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2810.