{
  "abstract": "Background Our previous findings of CTONG1104 suggested the frequent and reduced usage of some specific TCR sequences predicted favorable clinical outcomes for resected EGFR-mutant NSCLC patients who were treated with adjuvant EGFR-TKI or chemotherapy. 1 2 However, little is known about the identified TCR clones that belongs to which T cell subsets, and how they play a role in patients‘ pathological response to neoadjuvant immunotherapy.Methods In this study, we included all the selected TCR rearrangements with positive (n=7) and negative (n=4) predictive value in CTONG1104 and used them for prognostic analysis in CTONG1804. 3 Thus, scRNA/TCR sequencing was used to characterize the TCR sequence associated with the efficacy of neoadjuvant nivolumab and confirm their belonging T cell subsets.Results Among them, the frequency of Vβ24-1Jβ2-1 and Vβ29-1Jβ2-7 were significantly higher in MPR/pCR subgroup than those in non-MPR group. The combination of Vβ24-1Jβ2-1 and Vβ29-1Jβ2-7 presented the best model in predicting pathological response to neoadjuvant immunotherapy. The risk score was calculated and had a good performance in evaluating MPR/pCR (AUC = 70%, 95%CI: 53%-87%, P = 0.032). To balance the impact of clinical information on risk score, sex, age, and other clinical pathological characteristics were included in univariate and multivariate logistic regression analysis. The results indicated that risk score was an independent predictor for MPR/pCR. Among the 5 patients with baseline samples, the frequency of Vβ24-1Jβ2-1 and Vβ29-1Jβ2-7 was higher in the MPR/pCR subgroup compared to the non-MPR subgroup. In the four paired samples, there was no significant difference in the frequency of Vβ24-1Jβ2-1 and Vβ29-1Jβ2-7 before and after immunotherapy. A clear trend suggested that low-risk score was associated with favorable EFS. For scRNA/TCR sequencing, a total of 66,809 quality-controlled T cells were used for subsequent analysis. T cell clusters were annotated as CD4+ and CD8+ T cells. T cells were divided into two subgroups: exhausted (T_cell_Exh) and non-exhausted T cells (non_T_cell_Exh). Vβ24-1Jβ2-1 were mainly localized in non-exhausted T cells (including CD4_Tn, Treg, CD4_CD69, CD8_Trm, CD8_pre-Trm, CD8_TE and MAIT) in MPR/pCR group rather than in exhausted T cells. This result was also observed in Vβ29-1Jβ2-7 clones.Conclusions In the exploratory analysis of the CTONG1804 trial, Vβ24-1Jβ2-1 and Vβ29-1Jβ2-7 were associated with MPR/pCR and favorable clinical outcomes for stage II/III NSCLC patients underwent neoadjuvant immunotherapy. Vβ24-1Jβ2-1 and Vβ29-1Jβ2-7 were mainly localized in non-exhausted T cells. Vβ24-1Jβ2-1+ or Vβ29-1Jβ2-7+ T cells may serve as immune biomarkers for NSCLC in the treatment settings of neoadjuvant ICI.Acknowledgements We are grateful to the patients and families involved in this study. This work was supported by Bristol-Myers Squibb, Guangdong Provincial Key Lab of Translational Medicine in Lung Cancer. The funding sources had no role in the preparation of this manuscript.Trial Registration NCT04015778References Chen C, Liu SM, Chen Y, et al. Cancer Immunol Immunother. 2022;72:1261–1272.Chen C, Liu SM, Chen Y, et al. JCI Insight. 2022;7:e152631.Liu SY, Dong S, Yang XN, et al. Signal Transduct Target Ther. 2023;8:442.Ethics Approval The study was conducted in accordance with the Declaration of Helsinki and the Good Clinical Practice, and approved by the clinical research ethics committee of each participating center. All patients provided written informed consents prior to enrollment.Consent Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.",
  "authors": [
    {
      "affiliations": [
        "Guangdong Lung Cancer Institute, Guangdong Provincial People‘s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China"
      ],
      "name": "Si-Yang Maggie Liu"
    },
    {
      "affiliations": [
        "Department of Hematology, Guangzhou First People’s Hospital, Institute of Blood Transfusion and Hematology, Guangzhou Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Cunte Chen"
    },
    {
      "affiliations": [
        "Experimental Teaching Center of Functional Science of Basic Medicine, School of Basic Medicine and Public Health, Jinan University, Guangzhou, Guangdong, China"
      ],
      "name": "Yi-Kai Zhang"
    },
    {
      "affiliations": [
        "Guangdong Lung Cancer Institute, Guangdong Provincial People‘s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China",
        "Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Song Dong"
    },
    {
      "affiliations": [
        "Guangdong Lung Cancer Institute, Guangdong Provincial People‘s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China",
        "Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Xue-Ning Yang"
    },
    {
      "affiliations": [
        "Guangdong Lung Cancer Institute, Guangdong Provincial People‘s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China",
        "Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Qing Zhou"
    },
    {
      "affiliations": [
        "Guangdong Lung Cancer Institute, Guangdong Provincial People‘s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China",
        "Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Wen-Zhao Zhong"
    },
    {
      "affiliations": [
        "Guangdong Lung Cancer Institute, Guangdong Provincial People‘s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China",
        "Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Yi-Long Wu"
    },
    {
      "affiliations": [
        "Guangdong Lung Cancer Institute, Guangdong Provincial People‘s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China"
      ],
      "name": "Si-Yang Liu"
    },
    {
      "affiliations": [
        "Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, Guangdong, China"
      ],
      "name": "Yangqiu Li"
    }
  ],
  "title": "511 Specific TCR clones associated with better pathological response for early stage NSCLC patients treated with neoadjuvant immunotherapy: results from CTONG1804",
  "uid": "51ce34e7-b335-558d-ad4f-f88360055047"
}