Primary cilium (PC) is considered to represent a functional homologue of the immune synapse due to morphological and functional similarities in architecture. Both microtubule structures, i.e. primary cilia of cancer-associated fibroblasts and immune synapses between cytotoxic CD8+ tumor infiltrating lymphocytes (TILs) and antigen-presenting or cancer cells, are regularly found in varying amounts in the microenvironment of solid tumors. These could, in fact, represent two sides of the same coin. However, so far both parameters have not been evaluated simultaneously within the same group of patients.
The presence of PC in cells, programmed cell death protein-1 receptor (PD-1) expression and the frequency of intraepithelial CD8+ TILs was retrospectively evaluated in tumor tissue blocks of the resected specimens of the kidney in 104 patients with renal cell carcinoma of clear-cell type, 71 males and 33 females, with a median age of 64 years (range 38-82 years). Twenty-eight patients had stage I, 15 stage II, 31 stage III and 30 patients had stage IV tumor. Grade was as follows: grade 1 in 27 patients, grade 2 in 15 patients, grade 3 in 31 patient and grade IV in 30 patients.
The median frequency of PC was 0.0028% (0-0,0465%). The frequency of intraepithelial CD8+ TILs was negative in 1 patient, <25% in 63, 26-50% in 29 and 26-50% in 11, respectively. The expression of PD-1 was <5% in 52 patients, 5-25% in 34 patients, 26-50% in 13 patients, 51-75% in 4 patients and 75% in 1 patient. During the follow-up, recurrence occurred in 42 patients and 43 patients died. Median PFS was 44% (95% CI: 34-67%) and median OS was 98% (95% CI: 84-117%).
The present study provides the first data on the potential association frequency of PC, PD-1 and CD8+ TILs in patients with renal cancer.
Clinical trial identification
Legal entity responsible for the study
MH CZ-DRO (TH, 0064190).
MH CZ-DRO (TH, 0064190) and Ministry of Defense of the Czech Republic - long-term organization development plan Medical Aspects of Weapons of Mass Destruction of the Faculty of Military Health Sciences, University of Defense.
All authors have declared no conflicts of interest.