Immunotherapy has been considered a promising anticancer therapy of multiple tumors. Nevertheless, the really is that there is a lack of considerations and studies for metastatic cancers.
We have tried to establish the technology platforms for metastatic cancer immunotherapies. First, we had to know importance of the immune microenvironment with metastatic tumors. For this, we have tried to analysis for tumor-infiltrating lymphocytes and tertiary lymphoid structures in the primary breast tumors and metastatic sites in order to understand about tumor immune environments at various metastatic sites or between primary breast tumors and metastatic sites. Three hundred and thirty-five patients with metastatic breast cancers in the lung, liver, brain, or ovary, with available
hematoxylin and eosin-stained slides of metastatic sites (biopsy, n = 172; excision, n = 163), who were treated at the Asan Medical Center from January 2000 to March 2017, were included. Among the 335 cases, hematoxylin and eosin-stained slides of primary breast cancer were also available for evaluating tumor-infiltrating lymphocytes and tertiary lymphoid structures for 245 cases (biopsy, n = 37; excision, n = 208). Our results showed that metastatic breast tumors in the lung had more tumor-infiltrating lymphocytes than did tumors at other sites and matched primary tumors. In addition, the presence of tertiary lymphoid structures in metastatic sites is a critical factor for the level of tumor-infiltrating lymphocytes. These results suggested that immunotherapy would be useful for metastatic cancers.
Based on these results, we have planned to establish the technology platforms for identification of tumor specific antigen using metastatic tumor tissues. For this, we have collected the metastatic cancer tissues and matched adjacent normal tissue for analysis of somatic mutations and immunopeptidome. At the same time, we have tried to develop tumor specific antigen analysis method using data of whole genome sequencing and whole transcriptome sequencing with human leukocyte antigen peptidome data obtained from Liquid chromatography–mass spectrometry.
Ultimately, this study could provide a useful strategy for identifying tumor specific antigen which can be used cancer vaccine or/and tumor specific antigen responsive T-cell production for metastatic cancer immunotherapy.