Systematic immune reprogramming via PD-1 inhibition enhances early-stage lung cancer survival.

UID: 10798

Author(s): Mittal, Vivek*, Markowitz, GJ * MSK affiliated

Description: Summary from the GEO: "Success of immune checkpoint inhibitors in advanced non-small cell lung cancer (NSCLC) has invigorated their use in neo-adjuvant setting for early-stage disease. However, the cellular and molecular mechanisms of the early immune responses to therapy remain poorly understood. Through an integrated analysis of early-stage NSCLC patients and a Kras-mutant mouse model, we show a prevalent programmed cell death 1/ programmed cell death 1 ligand 1 (PD-1/PD-L1) axis exemplified by increased intratumoral PD-1+ T cells and PD-L1 expression. Notably, tumor progression was associated with spatiotemporal modulation of the immune microenvironment. Importantly, PD-1 inhibition controlled tumor growth, improved overall survival, and reprogrammed tumor-associated lymphoid and myeloid cells. Depletion of T lymphocyte subsets demonstrated synergistic effects of those populations on PD-1 inhibition of tumor growth. Transcriptome analyses revealed T cell subset-specific alterations corresponding to degree of response to the treatment. These results provide insights into temporal evolution of the phenotypic effects of PD-1/PD-L1 activation and inhibition, and motivate targeting this axis early in lung cancer progression.
CD4 and CD8 lung tumor infiltrating lymphocytes were sorted into RLT lysis buffer from IgG antibody or anti-PD1 antibody treated C57Bl/6 mice at day 14, 17 or 24 for mRNA-Sequencing."

Subject of Study

Subject(s)

OncoTree Cancer Type(s)

Non-Small Cell Lung Cancer

Access via GEO
Raw and TAR sequencing data.
Accession #: GSE114300

Access via SRA
RNA-Sequence reads for 64 samples.
Accession #: SRP145321

Access via BioProject
Additional information about overall initiative.
Accession #: PRJNA470891
Access Restrictions: Free to All
Access Instructions: The NCBI Gene Expression Omnibus, SRA, and BioProject databases provide open access to these files.
Associated Publications: Zhigalova EA, Izosimova AI, Yuzhakova DV, et al. RNA-Seq-Based TCR Profiling Reveals Persistently Increased Intratumoral Clonality in Responders to Anti-PD-1 Therapy. Front Oncol. 2020;10:385. Published 2020 Apr 28.
Data Type: Genomic
Equipment Used: Illumina HiSeq 4000
High throughput gene sequencing system
Dataset Format(s): Plain Text, SRA, TAR, RAW
Dataset Size: 7.1 Mb (TAR of TXT), SRA distributed across 36 files of 1-5 Gb each.

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