“Opportunities and obstacles for immunotherapy of cancer”

Dr. Nitya G. Chakraborty
Associate professor of Medicine
University of Connecticut School of Medicine
Connecticut, USA

11th January 2019
12.00 noon

at CDFD Lecture Hall, 3rd Floor,
Lab Building.

Recently blocking of Checkpoint inhibitors, anti PD1 and anti CTLA4, have revolutionized the immunotherapy of cancer. We see about 60% total response and prolonged survivals of patients treated with checkpoint inhibitors’ blockers. We have used this therapeutic protocol and got remarkable results in a small group of metastatic melanoma patients. Patients got remission of disease for a reasonable period but came back to the clinic with distant metastasis, mainly in the liver. From the biopsy tissue from liver we grew tumor and infiltrating lymphocyte in culture. We detected significant number of CD4+CD25+FoxP3+ CTLA4+ Treg cells in the cultures after expansion of tissue-derived cells. In connection with this study we did analyzed in vitro, 12 HLA A2 positive metastatic melanoma patients for the induction of melanoma antigen Mart-1 peptide specific CD8+CTL with autologous dendritic cell pulsed with the peptide, using PBL from the patients. Specific CD8+CTL induction was successful from all the 12 patients but those CTLs did not persist in the cultures for more than three weeks. CTLs were lost with a concomitant expansion of CD4+Treg cells. The induced Tregs were found to be very specific in blocking the induction of Mart-1 specific CTL response in separate cultures but failed to block the induction of Flu specific CTL in identical cultures. These findings indicate a specific activation of induced Tregs (iTregs) that might persist in the periphery and create further metastasis. Hence recent protocol for immunotherapy needs to be revisited and along with checkpoint blockers Treg induction also needs to be blocked.