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Poster Display session

337 - Anti-PD1 therapy increases peripheral blood NKT cells and chemokines in metastatic melanoma patients

Date

14 Dec 2018

Session

Poster Display session

Presenters

Henna Hakanen

Citation

Annals of Oncology (2018) 29 (suppl_10): x1-x10. 10.1093/annonc/mdy493

Authors

H. Hakanen1, M. Hernberg2, S. Mäkelä2, B. Yadav1, O. Brück1, S. Juteau3, L. Kohtamäki2, M. Ilander1, S. Mustjoki1, A. Kreutzman1

Author affiliations

  • 1 Hematology Research Unit Helsinki, University of Helsinki and Department of Hematology, 00290 - Helsinki/FI
  • 2 Department Of Oncology, Helsinki University Central Hospital Comprehensive Cancer Center, 00290 - Helsinki/FI
  • 3 Department Of Pathology, Helsinki University Central Hospital Comprehensive Cancer Center, 00290 - Helsinki/FI
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Resources

Abstract 337

Background

Anti-PD1 therapy has proven to be effective in various cancer types, but the overall impact of the treatment on the immune system is not yet fully understood. Therefore, we aimed in this study to discover the effects of anti-PD1 therapy on the immune system, especially on NK and NKT cells, which are less studied, but known to be involved in antitumor immune events.

Methods

Peripheral blood from immuno-oncology naive metastatic melanoma patients (n = 19) were obtained before the first infusion of anti-PD1, then 1 and 3 months later. From each time-point, complete blood counts (CBC) were obtained, and comprehensive immunophenotyping of NK, NKT, and T cells was performed. Also, 92 serum cytokines were measured using the Olink inflammation panel.

Results

Patients were categorized into two cohorts: responders (R, n = 6, PFS=17.0 months) and progressive disease (PD, n = 9, PFS=5.0 months). 4 patients were excluded due to challenging clinical evaluation of response. CBC indicated a significant decrease in the mean frequency of lymphocytes in PD but not in the R cohort. The responders had also higher frequency of lymphocytes at 1- and 3-month time points and lower frequency of neutrophils before initiation and after 1 and 3 months of treatment. The CBC absolute counts revealed that the responders had less neutrophils and monocytes after 3 months of treatment when compared to PD. Immunophenotyping revealed no changes in the frequency of T and NK cells during treatment, however the frequency of NKTbrightcells increased significantly. Moreover, R had more NKTdimcells before and after 3 months of therapy. Also, cytotoxic CD56dimNK cells expressed increased CD25 and CD45RO after 1 month of therapy. The cytokine assay indicated that anti-PD1 significantly increased the levels of CXC-family cytokines in the serum; CXCL9, CXCL11, CXCL10. Also, IL-12B and TNFRSF9 levels were increased. Further comparison of the two cohorts showed that CXCL9 was only increased in R cohort.

Conclusions

Anti-PD1 therapy increases the levels of NKT cells, inflammation related chemokines in blood and the expression of markers linked to enhanced cytotoxicity of NK cells. Therefore, further studies to investigate the role of NK and NKT cells in anti-PD1 induced responses are warranted.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

Anna Kreutzman.

Funding

Academy of Finland, Cancer Society of Finland, Sigrid Juselius Foundation.

Disclosure

M. Hernberg, S. Mäkelä, L. Kohtamäki: Trial funding: MSD, BMS, Amgen. S. Mustjoki: Honoraria, research funding: Novartis, Bristol-Myers Squibb, Ariad, Pfizer. All other authors have declared no conflicts of interest.

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