Cellular milieu in clear cell renal cell carcinoma

Abstract

Clear cell renal cell carcinoma (ccRCC) is globally the most prevalent renal cancer. The cells of origin in ccRCC have been identified as proximal tubular epithelial cells (PTEC); however, the transcriptomic pathways resulting in the transition from normal to malignant PTEC state have remained unclear. Immunotherapy targeting checkpoints have revolutionized the management of ccRCC, but a sustained clinical response is achieved in only a minority of ccRCC patients. This indicates that our understanding of the mechanisms involved in the malignant transition and resistance to immune checkpoint therapy in ccRCC is unclear. This review examines recent single-cell transcriptomics studies of ccRCC to clarify the transition of PTEC in ccRCC development, and the immune cell types, states, and interactions that may limit the response to targeted immune therapy, and finally suggests stromal cells as key drivers in recurrent and locally invasive ccRCC. These and future single-cell transcriptomics studies will continue to clarify the cellular milieu in the ccRCC microenvironment, thus defining actional clinical, therapeutic, and prognostic characteristics of ccRCC.

Dysregulated ANLN reveals immune cell landscape and promotes carcinogenesis by regulating the PI3K/Akt/mTOR pathway in clear cell renal cell carcinoma

“…The crosstalk between TME and cancer cells has attracted considerable research interest [ 44 , 45 ]. We found that ANLN expression in patients with ccRCC was positively correlated with stromal, immune, and ESTIMATE scores ( Fig.…”

High risk clear cell renal cell carcinoma microenvironments contain protumour immunophenotypes lacking specific immune checkpoints

“…This classification of exhausted/pro-tumour or non-exhausted/anti-tumour immune cell states is not static. Indeed, a spectrum of immune cell states is being recognised 60 . However, for brevity, here we utilised exhausted or non-exhausted states for five CD8 + T-cell sub-types and pro- or anti-tumour states for five TAM and tissue-resident monocyte sub-types identified within our ST-seq datasets (Table 1 ).…”

Inflammatory Networks in Renal Cell Carcinoma

“…An immune profiling study of human ccRCC samples, identified T cells as the main immune cell population, followed by myeloid cells, NKs and B cells. However, in contrast to many other solid tumor types, infiltration of CD8 + and CD4 + T cells in ccRCC tumors is often linked to a poor prognosis and advanced tumor grade [ 25 , 158 , 159 , 160 , 161 , 162 , 163 , 164 , 165 , 166 , 167 ], highlighting T cell dysfunction during the progression of RCC. Interestingly, the presence of lymphocytes positive for PD-1 and tumor cells positive for programmed cell death-ligand 1 (PD-L1) and/or PD-L2 in the invasive margin of ccRCC was correlated with the shortest DFS, OS and higher risk of post-surgical cancer progression [ 168 ].…”