Main Session
Sep
29
PQA 07 - Head and Neck Cancer, Lung Cancer/Thoracic Malignancies, and Nursing and Supportive Care
3544 - High Stress-Responsive T-cell Infiltration as a Prognostic Factor in Resectable NSCLC Treated with Neoadjuvant Immune-Chemotherapy
Presenter(s)
Yang Liu, RT - Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, jinan, shandong provinc
Y. Liu1, R. Gao1, Y. Chen2, and X. Meng1; 1Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China, 2Cancer Center, Shandong University, Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
Purpose/Objective(s):
To investigate stress-responsive T cells (TSTR), a newly identified T-cell state enriched in immunotherapy-resistant tumors. We aimed to determine whether TSTR infiltration could predict treatment response and prognosis in patients with resectable non–small cell lung cancer (NSCLC) receiving neoadjuvant immuno-chemotherapy.Materials/Methods:
A total of 181 resectable NSCLC patients receiving neoadjuvant immuno- chemotherapy were retrospectively enrolled, among whom paired pre- and post-treatment tumor tissue samples were obtained from 51 cases. Multiplex immunofluorescence (mIF) was used to simultaneously detect the expression of CD4, CD8, HSP70, and pan-CK in primary tumor lesions, and to quantitatively analyze the infiltration levels of CD4?T cells, CD8?T cells, CD8?TSTR and CD4?TSTR cells. We evaluated how target-cell infiltration relates to therapeutic response, clinicopathological attributes, and patient prognosis through correlation analyses and multivariate Cox regression.Results:
After neoadjuvant treatment, the infiltration levels of CD4?T cells, CD8?T cells, and their TSTR subsets in the tumor microenvironment (TME) all significantly increased. In the responder group, the CD4+TSTR/CD4+T cell ratio significantly decreased following treatment (P = 0.0008). Likewise, a significant reduction was observed in the CD8+TSTR/CD8+T cell ratio after treatment (P = 0.0002). The post-treatment infiltration levels of CD4?TSTR cells (P = 0.0075) and CD8?TSTR cells (P = 0.0041) were both significantly higher in the non-responder group than in the responder group. Survival analysis showed that high infiltration of CD8?TSTR cells before treatment, as well as high post-treatment infiltration of HSP70? immune cells, CD8?TSTR cells, and a high CD8?TSTR/CD8?T cell ratio, were all associated with poor prognosis, whereas high post-treatment infiltration of CD4?T cells was associated with favorable prognosis. Multivariate Cox analysis confirmed that post-treatment CD4?T cell infiltration and the CD8?TSTR/CD8?T cell ratio were independent prognostic factors for event-free survival (EFS).Conclusion:
TSTR cells, particularly CD8?TSTR cells, are an important independent prognostic factor in the context of neoadjuvant immuno-chemotherapy. Post-treatment CD4?T cell density and the CD8?TSTR cell proportion can serve as independent prognostic indicators, which elucidates the prognostic value of a novel T cell subset and provides clues for refining personalized treatment strategies.