Peripheral blood t cell responses to immunotherapy related adverse events in metastatic non-small cell lung cancer.

Abstract

e21047 Background: There has been prospective and retrospective evidence for the onset of immunotherapy (IO) related adverse events (irAE) and efficacy of anti programmed death (PD1) and Programmed death Ligand 1(PD L1) antibodies. The incidence of irAE in these studies ranged anywhere from 30-44%. There have been attempts in the past to cluster irAEs into distinct subtypes by T cell profiling before and after immunotherapy. Identifying the trend of CD4/CD8 changes during irAE may aid in finding ways to mitigate the severe toxicities, so the benefits of immunotherapy can be extended to far more number of patients. Methods: We have collected blood samples from 20 patients of Non Small Cell Lung Cancer patients (NSCLC) before each cycle of immunotherapy with informed consent. We have measured the different inflammatory markers such as IL6, IL10 using ELISA and isolated cellular components such as CD4, CD8 T cells along with others using magnetic bead technique, from these samples in our research laboratory at East Carolina University. We have also collected clinical information including the adverse events with their (Common Terminology Criteria for Adverse events) CTCAE 5.0 grading, different cell counts and C- reactive Protein (CRP). Results: In the cohort of 20 patients, 9 experienced irAE, out of which 6 had grade 2, including thyroiditis, pneumonitis, dermatitis, cytokine release syndrome (CRS), 1 had grade 3 pneumonitis, 1 had grade 4 pneumonitis and 1 had grade 1 CRS. When we looked at the CD4/CD8 ratio before each cycle, the one prior to the incidence of the irAE had at least 30-40% drop in the ratio consistently although there were minor fluctuations in the ratio at other times in both directions. Conclusions: Although most irAEs can be treated and reversed with steroids and other immunosuppressive agents, prolonged immunosuppression can lead to reduced efficacy of IO and development of undue opportunistic infections. Experience with IO has shown that earlier initiation of immunosuppression shortens the required treatment. However, given the challenge in the subtility of the earlier presentation, therapies are frequently delayed. Hence, biomarker to identify the early manifestations is of critical importance for early intervention. Studies suggest there is clonal expansion of CD8 T cells preceding grade 2-3 irAEs. Studies also indicate that increased T cells in the tumor is indicative of response to immunotherapy. Our observation suggests that increased CD8 in proportion to CD4 in the peripheral blood precedes the onset of irAE. It is unclear as to how this leads to increased toxicity when the immunotherapy treatment works by affecting T cell function. One possible explanation is that the T cell response in the tumor tissue is beneficial, however, T cell response in the peripheral blood may indicate response against self antigens leading to toxicities in the form of irAE.