Biological Biomarkers of Response and Resistance to Immune Checkpoint Inhibitors in Renal Cell Carcinoma

Abstract

Renal cell carcinoma (RCC) represents around 2% of cancer-related deaths worldwide per year. RCC is an immunogenic malignancy, and treatment of metastatic RCC (mRCC) has greatly improved since the advent of the new immunotherapy agents, including immune checkpoint inhibitors (ICIs). However, it should be stressed that a large proportion of patients does not respond to these therapies. There is thus an urgent need to identify predictive biomarkers of efficacy or resistance associated with ICIs or ICI/Tyrosine kinase inhibitor (TKI) combinations; this is a major challenge to achieve precision medicine for mRCC in routine practice. To identify potential biomarkers, it is necessary to improve our knowledge on the biology of immune checkpoints. A lot of efforts have been made over the last decade in the field of immuno-oncology. We summarize here the main data obtained in this field when considering mRCC. As for clinical biomarkers, clinician and scientific experts of the domain are facing difficulties in identifying such molecular entities, probably due to the complexity of immuno-oncology and the constant adaptation of tumor cells to their changing environment.

Fumarate Hydratase Enhances the Therapeutic Effect of PD-1 Antibody in Colorectal Cancer by Regulating PCSK9

“…The results showed that Fh1 expression was not significantly related to P and FOXP3 expression (Figure 3I,J), whereas low Fh1 expression was related to decr CD8 expression (Figure 3K). These findings suggest that knockdown of FH inhibits C cell clonal expansion in CRC and reduces the therapeutic effect of PD-1 antibodies development of new molecular entities is helpful in improving the effect of immuno apy [12,13]. In the future, drugs related to FH might be beneficial to improve the prog of patients with CRC, which is worthy of further exploration.…”

“…These findings suggest that knockdown of FH inhibits CD8+ T cell clonal expansion in CRC and reduces the therapeutic effect of PD-1 antibodies. The development of new molecular entities is helpful in improving the effect of immunotherapy [12,13]. In the future, drugs related to FH might be beneficial to improve the prognosis of patients with CRC, which is worthy of further exploration.…”

“…Therefore, we propose that FH may regulate sensitivity to treatment with PD-1 antibodies in patients with CRC and that patients with CRC with low FH expression may benefit from combined treatment with PCSK9 inhibitors and PD-1 antibodies. In addition, targeting key molecular entities in tumors can help maximize therapeutic efficacy [12,13], and FH has the potential in this regard.…”

Immunotherapy of Clear-Cell Renal-Cell Carcinoma

“…Therefore, the hypothesis that fecal microbiota transplantation or the manipulation of its composition can decrease the development of ICI resistance, thereby increasing the efficacy of this class of immunotherapy, has arisen. Currently, clinical trials are ongoing to validate these possible strategies [ 64 ].…”