Tertiary lymphoid structure-related immune infiltrates in NSCLC tumor lesions correlate with low tumor-reactivity of TIL products.
Détails
ID Serval
serval:BIB_4F0F8DC467FB
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Tertiary lymphoid structure-related immune infiltrates in NSCLC tumor lesions correlate with low tumor-reactivity of TIL products.
Périodique
Oncoimmunology
ISSN
2162-402X (Electronic)
ISSN-L
2162-4011
Statut éditorial
Publié
Date de publication
2024
Peer-reviewed
Oui
Volume
13
Numéro
1
Pages
2392898
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
Résumé
Adoptive transfer of tumor infiltrating lymphocytes (TIL therapy) has proven highly effective for treating solid cancers, including non-small cell lung cancer (NSCLC). However, not all patients benefit from this therapy for yet unknown reasons. Defining markers that correlate with high tumor-reactivity of the autologous TIL products is thus key for achieving better tailored immunotherapies. We questioned whether the composition of immune cell infiltrates correlated with the tumor-reactivity of expanded TIL products. Unbiased flow cytometry analysis of immune cell infiltrates of 26 early-stage and 20 late-stage NSCLC tumor lesions was used for correlations with the T cell differentiation and activation status, and with the expansion rate and anti-tumor response of generated TIL products. The composition of tumor immune infiltrates was highly variable between patients. Spearman's Rank Correlation revealed that high B cell infiltration negatively correlated with the tumor-reactivity of the patient's expanded TIL products, as defined by cytokine production upon exposure to autologous tumor digest. In-depth analysis revealed that tumor lesions with high B cell infiltrates contained tertiary lymphoid structure (TLS)-related immune infiltrates, including BCL6 <sup>+</sup> antibody-secreting B cells, IgD <sup>+</sup> BCL6 <sup>+</sup> B cells and CXCR5 <sup>+</sup> BLC6 <sup>+</sup> CD4 <sup>+</sup> T cells, and higher percentages of naïve CD8 <sup>+</sup> T cells. In conclusion, the composition of immune cell infiltrates in NSCLC tumors associates with the functionality of the expanded TIL product. Our findings may thus help improve patient selection for TIL therapy.
Mots-clé
Humans, Carcinoma, Non-Small-Cell Lung/immunology, Carcinoma, Non-Small-Cell Lung/pathology, Lung Neoplasms/immunology, Lung Neoplasms/pathology, Tertiary Lymphoid Structures/immunology, Tertiary Lymphoid Structures/pathology, Lymphocytes, Tumor-Infiltrating/immunology, Immunotherapy, Adoptive/methods, Female, Male, B-Lymphocytes/immunology, B-Lymphocytes/pathology, Middle Aged, Aged, Immune infiltrate, NSCLC, TIL therapy, TLS formation
Pubmed
Open Access
Oui
Création de la notice
30/08/2024 15:48
Dernière modification de la notice
03/10/2024 6:06