Abstract 3876: Multiplex immunohistochemistry accurately defines the immune compositional change of tumor microenvironment to predict hyperprogressive disease

Abstract

Abstract Introduction: To retrospectively assess hyperprogressive disease(HPD) in patients who underwent immune checkpoint blockade therapy and explore the heterogenous nature of tumor microenvironment of hyperprogressive patients using multiplex immunohistochemistry. Method: We retrospectively reviewed medical records of non-small cell lung cancer patients (n=243) treated with anti-PD-1 or anti-PD-L1 monotherapy at 5 institutes of St. Mary's Hospitals between January 2014 and May 2018. HPD was defined as a tumor growth kinetics ratio (TGKr) exceeding two during anti-PD-1 / PD-L1 therapy and a time-to-failure (TTF) of less than 2 months. We also analyzed the association of Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and CRP-albumin ratio (CAR) with HPD. To evaluate the difference of immune composition in TME by multiplex IHC(mIHC). Panel 1/2 composed of T cell markers and co-inhibitory signal markers. Panel 3/4 examined macrophages, NK cells and dendritic cells. Results: Overall, 231 patients were included. Overall, 26 patients (11.3%) met the criteria for hyperprogression. Multiplex IHX data quantitated immune subset number present intra-tumor vs the tumor stroma. there was a difference in immune cell composition between the HPD, poor responders (PRs) and good responders (GRs). High levels of CD4 + Teff cells, FOXP3 Treg cells were associated with HPD(p < 0.052, <0.017) and CD4 to CD45RO ratio indicated a potential predictive value to develop HPD(p < 0.042). Key observation was that there was a tendency to M2 polarization in patients with HPD when the macrophage M1/2 markers of CD14, CD68 and CD163 were observed. And the myeloid markers, such as CD11c, expressed by CAFs, tend to increase in the intra-tumor lesion of the HPD group (p < 0.501). Conclusion: This study was important in investigating the HPD-related immune prognostic factors in NSCLC patients in korea. According to these data, HPD is a unique biologic process distinct from a non HPD-PR. Multiplex IHC can be used not only to predict HPD, but also to understand the dynamicity and the complexed immune compositional change within TME. Furthermore, based on these findings, we are undergoing study the TME by serially collected pre- and post-treatment tissue samples, it may be helpful to shed light on the mechanisms of HPD. Citation Format: Seoree Kim, Sang Hoon Chun, Sang-Yeob Kim, Junyoung Seo, Chan Kwon Jung, Jinhyoung Kang. Multiplex immunohistochemistry accurately defines the immune compositional change of tumor microenvironment to predict hyperprogressive disease [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3876.