Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Proffered Paper session: Basic science & translational research

1660O - Dual immune checkpoint blockade induces analogous alterations in the intratumoral CD8+ T cell and Treg compartments

Date

11 Sep 2022

Session

Proffered Paper session: Basic science & translational research

Topics

Tumour Immunology;  Translational Research;  Immunotherapy

Tumour Site

Head and Neck Cancers

Presenters

Joleen Traets

Citation

Annals of Oncology (2022) 33 (suppl_7): S758-S771. 10.1016/annonc/annonc1078

Authors

J.J.H. Traets1, A.M. van der Leun2, J.L. Vos3, J.B.W. Elbers4, S. Patiwael5, X. Qiao1, M. Machuca-Ostos1, D.S. Thommen2, J.B.A.G. Haanen6, T.N. Schumacher2, C.L. Zuur7

Author affiliations

  • 1 Tumor Biology & Immunology, NKI-AVL - Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, 1066 CX - Amsterdam/NL
  • 2 Molecular Oncology And Immunology, NKI-AVL - Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, 1066 CX - Amsterdam/NL
  • 3 Head And Neck Oncology & Surgery, NKI-AVL - Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, 1066 CX - Amsterdam/NL
  • 4 Department Of Radiation Oncology, Erasmus University Medical Center, 3015 GD - Rotterdam/NL
  • 5 Biotherapeutics Unit, NKI-AVL - Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, 1066 CX - Amsterdam/NL
  • 6 Medical Oncology Dept, NKI-AVL - Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, 1066 CX - Amsterdam/NL
  • 7 Head And Neck Surgery Department, Netherlands Cancer Institute, 1066 CX - Amsterdam/NL
More

Resources

Login to access the resources on OncologyPRO.

Abstract 1660O

Background

Immune checkpoint blockade therapies have shown clinical activity in a range of human cancer types. While the capacity of T cells to recognize tumor antigens appears a critical driver of therapy response, the alterations in T cell state that are associated with response to immune checkpoint blockade are not well understood.

Methods

To dissect the effect of neoadjuvant PD-1 and CTLA4 blockade on the intratumoral T cell population in head and neck squamous cell carcinoma (HNSCC), we performed single cell RNA and TCR sequencing on the immune infiltrates of HNSCC samples derived from treatment-naïve patients that were enrolled in the IMCISION trial treated with neoadjuvant Nivolumab (anti-PD1, 3 mg/kg, weeks 1&3) and Ipilimumab (anti-CTLA4, 1mg/kg, week 1) prior to surgery (week 4). The intratumoral T cell population was analyzed in matched pre- and on-treatment tumor biopsies from 1 partial (PR) and 10 major pathological responding (MPR) patients and 7 non-responding patients. MPR was defined as ≤10% and PR was defined as ≤50% but >10% residual viable cancer cells in the surgical resection specimen.

Results

At baseline, a subset of 4-1BB+ regulatory CD4+ T cells (activated Tregs) was more abundant in responding than non-responding tumors. Furthermore, upon therapy, this activated Treg population showed a profound decrease in responding patients. In an analogous process, intratumoral dysfunctional T cells in the CD8+ T cell compartment transitioned to a state of reduced activity and reduced dysfunction upon therapy. Next to these concurrent changes in the activated Treg and dysfunctional CD8+ compartments, the abundance of a separate transitional CD8+ T cell population with low levels of dysfunction increased substantially upon therapy, presumably because of increased T cell entry.

Conclusions

Together, these data demonstrate that the presence of an activated Treg compartment at baseline may predict response to dual PD-1 and CTLA4 blockade in HNSCC, and that this combination therapy results in a parallel remodeling of both the intratumoral Treg and dysfunctional CD8+ T cell compartments.

Clinical trial identification

Vos et al. Nat Commun. 2021 Dec 22;12(1):7348, NCT04620200.

Editorial acknowledgement

Legal entity responsible for the study

The Netherlands Cancer Institute (NKI) (Antoni van Leeuwenhoek), Charlotte L. zuur.

Funding

Bristol Myers Squibb (BMS).

Disclosure

C.L. Zuur: Financial Interests, Institutional, Funding: Bristol Myers Squibb (BMS). All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.