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Active surveillance characterizes human intratumoral T cell exhaustion
- Source :
- J Clin Invest, The Journal of clinical investigation, vol 131, iss 18
- Publication Year :
- 2021
- Publisher :
- American Society for Clinical Investigation, 2021.
-
Abstract
- Intratumoral T cells that might otherwise control tumors are often identified in an ‘exhausted’ state, defined by specific epigenetic modifications as well as upregulation of genes such as CD38, CTLA-4 and PD-1. While the term might imply inactivity, there has been little study of this state at the phenotypic level in tumors to understand the extent of their incapacitation. Starting with the observation that T cells move more quickly through mouse tumors as residence time increases and they progress towards exhaustion, we elaborated a non-stimulatory live-biopsy method for real-time study of T cell behaviors within individual patient tumors. Using two-photon microscopy, we studied native CD8 T cells interacting with APCs and with cancer cells in different micro-niches of human tumors, finding that T cell speed was variable by region and by patient, was independent of T cell density and was inversely correlated with local tumor density. Across a range of tumor types, we found a strong relationship between CD8 T cell motility and exhausted T cell state that corresponds to observations made in mouse models where exhausted T cells move faster. While this is a small study, it demonstrates at least two types of T cell dynamic states in individual human tumors and supports the existence of an active program in ‘exhausted’ T cells that extends beyond incapacitating them.
- Subjects :
- T cell
Immunology
T cells
Motility
Biology
CD38
CD8-Positive T-Lymphocytes
Medical and Health Sciences
Mice
Experimental
Downregulation and upregulation
Cell Movement
Neoplasms
medicine
Immune Tolerance
Tumor Microenvironment
Cytotoxic T cell
Animals
Humans
Epigenetics
Lymphocytes
Tumor-Infiltrating
Cancer
Mammary Neoplasms
Concise Communication
Immunity
General Medicine
medicine.disease
Phenotype
medicine.anatomical_structure
Oncology
Cancer cell
Cancer research
Female
CD8
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- J Clin Invest, The Journal of clinical investigation, vol 131, iss 18
- Accession number :
- edsair.doi.dedup.....5d2375d382cc28c8b967bee1289668c7