Ding, Fei

Ferris, Robert L

Gibson, Sandra Poveda

Jie, Hyun-Bae

Kansy, Benjamin A

Lin, Yan

Journal for ImmunoTherapy of Cancer

PubMed

Ferris, Robert L.

Name not available

Anti-EGFR mAb cetuximab therapy increases T cell receptor (TCR) diversity in the peripheral blood and focuses TCR richness in the tumor microenvironment

Benjamin A Kansy

Yan Lin

Fei Ding

Sandra Poveda Gibson

Hyun-Bae Jie

Robert L Ferris

Crossref

D-Scholarship@Pitt

POSTER PRESENTATION Open AccessAnti-EGFR mAb cetuximab therapy increasesT cell receptor (TCR) diversity in the peripheralblood and focuses TCR richness in the tumormicroenvironmentBenjamin A Kansy1*, Yan Lin2, Fei Ding2, Sandra Poveda Gibson3, Hyun-Bae Jie3, Robert L Ferris3From 30th Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2015)National Harbor, MD, USA. 4-8 November 2015IntroductionT cell receptor (TCR) recognition of tumor antigen isessential for effective antitumor immunity. The immunesystem`s ability to respond to a broad spectrum of anti-gens requires a sophisticated selection of various TCR.So far, little is known about the role of TCR richness andclonality in the immune response to the EGFR-specificmAb, cetuximab. Therefore, we investigated differencesin TCR sequences between HPV+ and HPV- patients, aswell as differences in sequence characteristics betweenT cells of peripheral blood mononuclear cells (PBMC)and tumor infiltrating lymphocytes (TIL). Additionally,we were able to investigate the TCR richness and clonal-ity in samples pre- and post-treatment in a clinical singleagent cetuximab trial.Material and methodsTCR genotyping was performed and quantified by Adap-tive Technologies, Inc (Seattle, WA). Richness (S) wasdefined as total number of unique productive sequences.The Shannon Index is defined as H=-log∑pi(1-pi), pi isthe proportion of sequence i relative to the totalsequences. The clonality is defined as 1-H/log(S). Themaximum available number of samples from the samepatient was 4, containing pre- and post-treatment PBMCand pre- and post-treatment TIL. Paired comparisons(pre vs. post) were done using the Wilcoxon Signed Ranktests. Comparisons between two independent groups (i.e.HPV+ vs. HPV-, or responders vs. non-responders) wereaccomplished with Wilcoxon Rank Sum tests.ResultsUsing a cohort of neoadjuvant, single-agent cetuximabtreated HNSCC patients, 56 samples were analyzed forglobal TCR diversity. HPV+ and HPV- patients did notsignificantly differ in clonality and richness pre- andpost-treatment in either PBMC or TIL. However, cetuxi-mab therapy significantly increased the richness ofunique sequences in PBMC (p=0.0002). Most impor-tantly, the responder group had a higher increase ofrichness post-treatment in PBMC. The differencereached a p-value of 0.03 post-treatment. On the con-trary, this increase was not observed in TIL, whichappeared to be more focused after cetuximab therapy.DiscussionTCR clonality and richness for PBMC and TIL seem to beindependent from the patient’s HPV status in HNSCC.Intriguingly, an increase in richness of TCR sequences inthe periphery (PBMC) but a focusing in TIL was associatedwith an improved treatment response, suggesting an influ-ence of peripheral quantity on intratumoral TCR quality.Authors’ details1Department of Otorhinolaryngology, University Hospital Essen, Germany;University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA. 2BiostatisticsFacility, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.3University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.Published: 4 November 2015doi:10.1186/2051-1426-3-S2-P73Cite this article as: Kansy et al.: Anti-EGFR mAb cetuximab therapyincreases T cell receptor (TCR) diversity in the peripheral blood andfocuses TCR richness in the tumor microenvironment. Journal forImmunoTherapy of Cancer 2015 3(Suppl 2):P73.1Department of Otorhinolaryngology, University Hospital Essen, Germany;University of Pittsburgh Cancer Institute, Pittsburgh, PA, USAFull list of author information is available at the end of the articleKansy et al. Journal for ImmunoTherapy of Cancer 2015, 3(Suppl 2):P73http://www.immunotherapyofcancer.org/content/3/S2/P73© 2015 Kansy et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided theoriginal work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

http://d-scholarship.pitt.edu/29010/1/art%253A10.1186%252F2051-1426-3-S2-P73.pdf

Anti-EGFR mAb cetuximab therapy increases T cell receptor (TCR) diversity in the peripheral blood and focuses TCR richness in the tumor microenvironment

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