Abstract 1173: T cell receptor diversity in buffy coat samples from subsets of breast and ovarian cancer patients
Authors: Keup Corinna , Kolberg-Liedtke Cornelia , Tian Song , Rulli Samuel J. , Hauch Siegfried , Buderath Paul , Hoffmann Oliver , Kimmig Rainer , Kasimir-Bauer Sabine 
Published: March 2024

Abstract
Background: Immunotherapy, mainly by the use of immune checkpoint inhibitors (ICI), has been established as a standard option for both, solid tumors and hematological malignancies. Unfortunately, this success has only been replicated in a subset of patients (pts) with gynecological cancers. In ovarian cancer (OC), response rates to ICI monotherapy were low and in breast cancer (BC), only the subgroup of triple-negative BC (TNBC) pts showed an improved outcome by the addition of ICI. One reason for limited success of immunotherapy might be an impaired immune system. In this regard, monitoring the T cell receptor (TCR) repertoire could provide key insights into adaptive immune responses to ultimately understand disease initiation, progression and treatment response. Here we elucidated TCR alpha, beta, gamma and delta in buffy coats of pts with non-metastatic OC as well as non-metastatic and metastatic TNBC and compared the results with healthy donors (HDs).
Methods: RNA was isolated from buffy coat samples of 20 HDs, 10 treatment-naïve primary OC pts, 14 treatment-naïve, non-metastatic TNBC pts (participating in the phase II neomono trial) and 19 pts with metastatic TNBC by a modified QIAamp RNA Blood Mini protocol. A survey of the TCR diversity and mapping of common and unique TCRs was done using the QIAseq Targeted RNA Panel Human TCR panel for all known T-cell receptors (alpha, beta, gamma, delta).
Results: Regardless of the cancer entity, a significant reduction in TCR diversity was observed compared to HDs with the greatest differences observed in the delta receptors. When OC samples were compared with HDs, the difference in diversity was highly significant for all TCR subtypes (TCRalpha: p=0.013; TCRbeta: p=0.008; TCRgamma: 0.008; TCRdelta: 0.006). Similar results were obtained for non-metastatic TNBC (TCRalpha: p=0.0002; TCRbeta: p=0.0001; TCRgamma: p=0.002; TCRdelta: p=0.002) as well as metastatic TNBC patients (TCRalpha: p=0.001; TCRbeta: p=0.001; TCRgamma: p=0.005; TCRdelta: p=0.003) when their TCR diversity was compared to HDs. Interestingly, no significant differences in diversity were obtained when treatment-naïve non-metastatic TNBC pts were compared with heavily pretreated metastatic TNBC pts. The lowest diversity was found in BC pts compared to the OC pts.
Conclusion: We have initiated a survey of the TCR diversity in TNBC and OC patients. Further evaluations will include the correlation of these findings with clinical characteristics and outcome. Whether the reduced TCR diversity represents T cell exhaustion or T cell specialization cannot yet be deduced from the results. Nevertheless, the addition of a TCR diversity score could provide an additional metric which may help provide patient guidance when integrated into a multi-modal molecular test.
Citation Format: Corinna Keup, Cornelia Kolberg-Liedtke, Song Tian, Samuel J. Rulli, Siegfried Hauch, Paul Buderath, Oliver Hoffmann, Rainer Kimmig, Sabine Kasimir-Bauer. T cell receptor diversity in buffy coat samples from subsets of breast and ovarian cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1173.