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. 2025 Feb 24;25(1):333.
doi: 10.1186/s12885-025-13716-w.

Dynamic changes in immune repertoire profiles in patients with stage III unresectable non-small cell lung cancer during consolidation treatment with immunotherapy

Nareenart Iemwimangsa  1 , Dulyathat Anantaya  2   3 , Songporn Oranratnachai  4 , Thanaporn Thamrongjirapat  2   3 , Putthapoom Lumjiaktase  5 , View-Hune Teoh  6 , Khantong Khiewngam  7 , Nanamon Monnamo  8 , Pimtip Sanvarinda  9 , Pimpin Incharoen  5 , Angkana Charoenyingwattan  1 , Insee Sensorn  1 , Thitiya Dejthevaporn  2   3 , Ekaphop Sirachainan  2   3 , Wasun Chantratita  1 , Thanyanan Reungwetwattana  2   3 , Narumol Trachu  10
Affiliations

Dynamic changes in immune repertoire profiles in patients with stage III unresectable non-small cell lung cancer during consolidation treatment with immunotherapy

Nareenart Iemwimangsa et al. BMC Cancer. .

Abstract

Background: One-year of immune checkpoint inhibitor (ICI) treatment after concurrent chemoradiation (CCRT) in unresectable stage III non-small cell lung cancer (NSCLC) is a standard of care. The precise predictive biomarkers are under investigations either immunological markers or clinical characteristics. Here, we explored immune repertoire of T cell receptor β-chain (TCRβ) during ICI treatment.

Methods: During August 2019 and September 2021, stage III NSCLC, post CCRT patients from Ramathibodi Hospital was enrolled. All patients were treated by durvalumab after CCRT. Blood samples were collected together with clinical data and tumor assessment every 3-4 months until disease progression or discontinuation of treatment due to adverse events. CDR3 region and TCRΒ polymorphisms was explored by RNA sequencing using Next-Generation Sequencing (NGS) TCR beta short-read assay. Bioinformatic analysis was performed to analyze clonal diversity, TCR convergence frequency and the Shannon diversity from each timepoint. Immune repertoire and clinical correlation were explored using Spearman's correlation and Pearson's correlation. RStudio software version 2021 build 372 was used for analyses. A significance level was at P < 0.05.

Results: Forty-four blood samples from 12 patients were analyzed. Mean duration of durvalumab treatment was 284 days. After durvalumab treatment, increasing of TCR convergence frequency was found compared to baseline (R = 0.36). Interestingly, it was also significantly higher in non-progressive disease (non-PD) patients compared with progressive disease (PD) patients (P = 0.011). Furthermore, Shannon diversity was higher increasing in PD patients compared with non-PD patients. Taken together, our study found that increasing of TCR convergence with less T-cell diversity in non-PD patients probably demonstrated a T cell-specific clonal expansion response to durvalumab treatment in this population.

Conclusions: TCRβ repertoire is the potential biomarker for predicting durvalumab treatment response in post CCRT stage III NSCLC patients. However, a larger cohort with long-read assay should be explored.

Keywords: Immune repertoire; Immunotherapy; Stage III NSCLC; Stage III non-small cell lung cancer; TCR polymorphism.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The Human Research Ethics Committee of Ramathibodi Hospital, Mahidol University, Bangkok, Thailand, approved this study (IRB number COA. MURA2019/730). The study adhered to the Declaration of Helsinki to this effect in the ‘Ethics approval and consent to participate’ section or appropriate national guidelines. All methods were performed in accordance with the relevant guidelines and local regulations. Informed consent was obtained from all patients in this study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Blood sample collection schedule
Fig. 2
Fig. 2
Treatment scatterplot indicating the relationship between the PD and non-PD groups and dynamic changes in TCR convergence frequency according to treatment response by using the analysis Spearman correlation. PD: Progressive disease, TCR: T cell receptor
Fig. 3
Fig. 3
Changes in immune repertoire profiles during immunotherapy treatment between patients with progressive disease (red color) and non-progressive disease (green color). (A) Shannon diversity, (B) evenness, and (C) TCR convergence ratio. TCR: T cell receptor
Fig. 4
Fig. 4
Case study 1 with progressive disease showing the trend in CDR3 amino acid sequence frequencies changing over time with durvalumab treatment. CDR3: complementarity determining region 3
Fig. 5
Fig. 5
Case study 2 with non-progressive disease showing the trend in CDR3 amino acid sequence frequencies changing over time with durvalumab treatment. CDR3: complementarity determining region 3
Fig. 6
Fig. 6
Case study 3 with non-progressive disease showing the trend in CDR3 amino acid sequence frequencies changing over time with durvalumab treatment. CDR3: complementarity determining region 3
See this image and copyright information in PMC

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