T Cell Exhaustion: Phenomenon, Diagnostic and Prognostic Significance, Age-Related Features, and Correction in Lung Cancer.

Exhaustion of cytotoxic T cells was investigated in C57Bl/6 mice with modeled lung cancer. Differences in the formation of T cell exhaustion in orthotopic and metastatic lung cancer were identified. Regardless of the model, cancer stem cells (CSCs) contributed to the formation of hyporeactive T-cell phenotypes with low antitumor activity and survival in the context of tumor progression. A pilot study confirmed the role of CSCs and T cell exhaustion in tumor progression and metastatic disease in patients with small-cell lung carcinoma (SCLC). It is proposed to consider CSCs and exhausted T cells are proposed as predictors of progression and poor prognosis of SCLC. A novel approach to combat effector T cell exhaustion based on the regulation of PD-1/PD-L1 and MAPK/ERK signaling pathways was developed and tested in preclinical studies. The reprogramming efficiency has been demonstrated for both mouse and human T cells. A dedicated section of this work addresses the influence of aging on the effector T cell exhaustion and the choice of therapy for lung cancer under these conditions. Understanding and implementing these achievements will improve the treatment outcome and the quality of life for lung cancer patients from different age groups.