Congratulations to Institut Curie for the great work.
This case-report study identifies a patient with an unusual sensitivity to a programmed death protein 1 (PD-1) inhibitor, a pharmacological agent that relieves the immune suppression that occurs in certain types of cancer and prevents immune cells from attacking the growing tumor. This therapy belongs to a family of frontline drugs being implemented in cancer immunotherapy, working by boosting the patients’ immune system, allowing it to target and kill cancer cells.
This sensitivity to a PD-1 inhibitor was associated with other genetic mutations (changes in the DNA), including germline and somatic mutations — that is, respectively, mutations a patient is born with (and that may be passed down to subsequent generations), or mutations that a patient may develop after birth — in a gene encoding the Methyl-CpG-binding domain protein 4 (the MBD4 gene).
This study looked at the responses of 42 metastatic UM patients, and more specifically at one outlier patient who achieved an unusual complete response of known metastases with the PD-1 inhibitor pembrolizumab after having developed metastatic UM in the liver, lung and bone, and appearing to do so through stimulation of existing cell-mediated immunity against the UM tumor.
“The identification of two UM cases with MBD4 germline mutations is intriguing, and possibly related to the frequent monosomy 3—where MBD4 is located—in this disease. Integrating our institutional cohort and the TCGA UM cohort, MBD4 germline deleterious mutations were present in 2% of UM patients (2 out of 102)”.
Additional genetic analysis of the patient´s liver metastases — by whole-exome sequencing, where all the sections of the genome coding for a protein are sequenced — revealed somatic GNAQ and BAP1 mutations, as well as monosomy 3, genetic changes and a chromosome loss common in high risk uveal melanoma patient tumors.
You can find a link for the full paper here.