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Common phenotypic dynamics of tumor-infiltrating lymphocytes across different histologies upon checkpoint inhibition: impact on clinical outcome
- Source :
- Cytotherapy. 22:204-213
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- Background Immune checkpoint inhibitors (ICIs) have revolutionized the cancer therapeutic landscape and our perception of interactions between the immune system and tumor cells. Despite remarkable progress, disease relapse and primary resistance are not uncommon. Understanding the biological processes that tumor-infiltrating lymphocytes (TILs) undergo during ICI, how this affects the tumor microenvironment (TME) and, ultimately, clinical outcome is, therefore, necessary to further improve treatment efficacy. Aim In the current study, we sought to characterize TILs from patients with metastatic solid tumors undergoing ICI correlating flowcytometric findings with clinical outcome. Methods In total, 20 patients with 10 different metastatic solid tumors treated with ICIs targeting programmed-cell death-1 (PD-1)/PD-L1 axis were included in this study. The phenotype of T cells deriving from biopsies obtained prior to treatment initiation and on-treatment was investigaded. Analyses were focused on T cells’ degree of differentiation and activity and how they correlate with transcriptomic changes in the TME. Results Data indicate that patients benefitting from ICIs accumulate CD8+central memory T cells. TILs developed an effector-like phenotype over time, which was also associated with a cytolytic gene signature. In terms of modulation of T-cell responses, we observed that high expression of checkpoint molecules pre-treatment (i.e., PD-1, lymphocyte activation gene-3 [LAG-3], B and T-lymphocyte attenuator [BTLA] and T-cell immunoglobulin and mucin domain containing-3 [TIM-3]) was associated with similar gene signature and correlated to treatment benefit. Increasing expression of LAG-3 and BTLA in the CD8 compartment and their co-expression with PD-1 during treatment were, however, a common feature for patients who failed to respond to ICIs. Conclusions Besides identifying immune profiles suggestive of response to ICI, our results provide a more nuanced picture regarding expression of checkpoint molecules that goes beyond T-cell anergy.
- Subjects :
- Adult
Male
0301 basic medicine
Cancer Research
Biopsy
Programmed Cell Death 1 Receptor
Immunology
BTLA
CD8-Positive T-Lymphocytes
B7-H1 Antigen
03 medical and health sciences
Lymphocytes, Tumor-Infiltrating
0302 clinical medicine
Immune system
Neoplasms
Tumor Microenvironment
Humans
Immunologic Factors
Immunology and Allergy
Medicine
Molecular Targeted Therapy
Genetics (clinical)
Aged
Transplantation
Tumor microenvironment
business.industry
Tumor-infiltrating lymphocytes
Cancer
Cell Biology
Middle Aged
Gene signature
medicine.disease
Immune checkpoint
Phenotype
Treatment Outcome
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
Cancer research
Female
Immunotherapy
business
CD8
Follow-Up Studies
Subjects
Details
- ISSN :
- 14653249
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- Cytotherapy
- Accession number :
- edsair.doi.dedup.....3ce43c4cebebec27ff6a8d0c8e71cc0f