Bibliographic Details
| Title: |
Perioperative chemoimmunotherapy induces strong immune responses and long-term survival in patients with HLA class I-deficient non-small cell lung cancer |
| Authors: |
Ignacio I Wistuba, Amelia Insa, Mariano Provencio, Bartomeu Massutí, Federico Garrido, Edwin R Parra, Delvys Rodriguez-Abreu, Manuel Cobo, Joaquín Casal-Rubio, Ernest Nadal, Javier Martín-López, Diego Megías, Belén Sierra-Rodero, Alberto Cruz-Bermúdez, Alex Martinez-Marti, Isidoro Barneto Aranda, Santiago Viteri, Marta Casarrubios, Cristina Martinez-Toledo, Virginia Calvo, Marta Molina-Alejandre, Francisco Perea, Javier de Castro, Joaquín Mosquera Martínez, Rafael Muñoz-Viana, Natalia Aptsiauri, Francisco Ruiz-Cabello |
| Source: |
Journal for ImmunoTherapy of Cancer, Vol 12, Iss 10 (2024) |
| Publisher Information: |
BMJ Publishing Group, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| Subject Terms: |
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| More Details: |
Background Loss of human leukocyte antigen (HLA) class I expression and loss of heterozygosity (LOH) are common events implicated in the primary resistance of non-small cell lung cancer (NSCLC) to immunotherapy. However, there is no data on perioperative chemoimmunotherapy (ChIO) efficacy or response mechanisms in the context of HLA class I defects.Methods Baseline HLA class I tumor status (HLA-deficient (HLA-DEF) or HLA-proficient (HLA-PRO)) was determined by DNA LOH combined with immunohistochemistry for protein levels in tissue of 24 patients with NSCLC treated with perioperative nivolumab plus chemotherapy from NADIM trial (NCT03081689). We integrated HLA tumor status with molecular data (programmed death-ligand 1 (PD-L1), TMB, TCR repertoire, TILs populations, bulk RNA-seq, and spatial transcriptomics (ST)) and clinical outcomes (pathological response and survival data) to study the activity of perioperative ChIO considering HLA class I defects.Results HLA-DEF tumors comprised 41.7% of analyzed tumors and showed a desert-like microenvironment at baseline, with lower PD-L1 levels and reduced immune infiltrate. However, perioperative ChIO induced similar complete pathological response (CPR) rates in both HLA-DEF and PRO tumors (50% and 60% respectively, p=0.670), as well as 3-year survival rates: Progression-free survival (PFS) and overall survival (OS) of 70% (95% CI 32.9% to 89.2%) for HLA-DEF, and PFS 71.4% (95% CI 40.6% to 88.2%) and OS 92.9% (95% CI 59.1% to 99.0%) for HLA-PRO (log-rank PFS p=0.909, OS p=0.137). Proof-of-concept ST analysis of a CPR HLA-DEF tumor after ChIO showed a strong immune response with tertiary lymphoid structures (TLS), CD4+T cells with HLA class II colocalization, and activated CD8+T cells.Conclusions Our findings highlight the activity of perioperative ChIO, and the potential role of TLS and T-cell immune response, in NSCLC HLA-DEF tumors. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2051-1426 |
| Relation: |
https://jitc.bmj.com/content/12/10/e009762.full; https://doaj.org/toc/2051-1426 |
| DOI: |
10.1136/jitc-2024-009762 |
| Access URL: |
https://doaj.org/article/8c3f29b6cb394ac3ba9e2fc1ab852402 |
| Accession Number: |
edsdoj.8c3f29b6cb394ac3ba9e2fc1ab852402 |
| Database: |
Directory of Open Access Journals |
