Vanda Téglási1, János Bíró1, Luca Vass1, Ambrus Gángó1, Csaba Bödör1, Judit Moldvay2, 3, László Tiszlavicz4, József Furák5, József Tímár3, 6, Zoltán Szállási3, 7, 8, Lilla Reiniger1, 3
1: 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest
2: Department of Tumor Biology, National Korányi Institute of Pulmonology–Semmelweis University, Budapest
3: SE-NAP Brain Metastasis Research group, 2nd Department of Pathology, Semmelweis University, Budapest
4: Department of Pathology, University of Szeged, Szeged
5: Department of Surgery, University of Szeged, Szeged
6: Hungarian Academy of Sciences–Semmelweis University, Molecular Oncology Research Unit, 2nd Department of Pathology, Semmelweis University, Budapest
7: Computational Health Informatics Program, Boston Children’s Hospital, USA, Harvard Medical School, Boston, United States
8: Danish Cancer Society Research Center, Copenhagen, Denmark
Introduction: Several lines of evidence support that higher amount of tumor infiltrating lymphocytes (TIL) correlates with better prognosis. Cytotoxic T-cells are able to eliminate tumor cells via T-cell receptors (TCR) recognizing specific antigens expressed by tumor cells. Novel therapeutic approaches include agents increasing anti-tumor effect of immune cells or others blocking mechanisms that potentiate immune tolerance of tumor cells. Among these are immune checkpoint inhibitors which are in advanced clinical trials, however, patient selection criteria for immune checkpoint inhibitor therapy are still under debate. The PD-L1 expression of tumor cells is the only accepted biomarker, however, the TCR diversity of TIL may be more relevant to immune checkpoint inhibitor response.
Method: We analyzed 19 primary lung adenocarcinoma and corresponding brain metastasis samples. On H&E stained sections we determined the amount of lymphocytes within and around the tumor tissue to see if the sample is eligible for further analysis. For the determination of TCR diversity in the paired samples we performed fragment analysis with different primers after DNA isolation according to the BioMed2 protocol.
Results: Monoclonality was detected in 1 primary tumor and 3 brain metastasis samples. We observed change in the TCR clonality in 2 brain metastases compared to the corresponding primary lung adenocarcinoma. According to our results chemo- or steroid therapy alone appears not to disturb either the primary or metastatic tumor samples’ TCR diversity, however chemo- and steroid therapy together may induce change towards monoclonality in brain metastases compared to the corresponding primary lung adenocarcinoma.
Conclusion: In case of introducing the TCR diversity as predictor for check-point inhibitors, analysis of the metastatic tissue would be required before the treatment in advanced malignancies.
Supported BY the ÚNKP- -18-3-III-SE-33 New National Excellence Program of the Ministry of Human Capacities.
Doctoral School: Pathological Sciences
Program: Experimental Oncology
Supervisor: Lilla Reiniger MD, PhD
E-mail address: firstname.lastname@example.org