Early T Cell Signalling Is Reversibly Altered in PD-1+ T Lymphocytes Infiltrating Human Tumors
2011

Early T Cell Signalling Changes in Tumor-Infiltrating Lymphocytes

Sample size: 50 publication 10 minutes Evidence: moderate

Author Information

Author(s): Wang Shu-Fang, Fouquet Stéphane, Chapon Maxime, Salmon Hélène, Regnier Fabienne, Labroquère Karine, Badoual Cécile, Damotte Diane, Validire Pierre, Maubec Eve, Delongchamps Nicolas B., Cazes Aurélie, Gibault Laure, Garcette Marylène, Dieu-Nosjean Marie-Caroline, Zerbib Marc, Avril Marie-Françoise, Prévost-Blondel Armelle, Randriamampita Clotilde, Trautmann Alain, Bercovici Nadège

Primary Institution: Inserm, U1016, Institut Cochin, Paris, France

Hypothesis

The study investigates how early T cell receptor (TCR) signaling is altered in tumor-infiltrating lymphocytes (TIL) and the role of PD-1 in this process.

Conclusion

The study found that TIL exhibit significant alterations in early TCR signaling pathways, which can be partially reversed after tumor dissociation.

Supporting Evidence

  • TIL showed a significant reduction in calcium response compared to peripheral blood T cells.
  • Phosphorylation of Akt was severely affected in TIL, showing a 15-fold reduction compared to peripheral blood T cells.
  • PD-1 was frequently expressed on TIL, indicating a chronic activation state.
  • Recovery of TIL function was observed within hours after tumor dissociation.

Takeaway

T cells that are found in tumors don't work as well as they should because of changes in how they signal, but they can get better if the tumor environment is changed.

Methodology

The study analyzed the functional state of TIL from three types of tumors immediately after resection, focusing on calcium, Akt, and ERK signaling pathways.

Potential Biases

Potential bias in patient selection and tumor types analyzed.

Limitations

The study primarily focuses on TIL from specific tumor types and may not generalize to all cancers.

Participant Demographics

Patients with non-small cell lung carcinoma (NSCLC), melanoma, and renal cell carcinoma (RCC).

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pone.0017621

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