Abstract 317P
Background
Bladder cancer was recently classified at the molecular level, including a detailed analysis conducted on oncogene mutations and immune activity in the tumor microenvironment. However, the association between oncogene mutations and the tumor microenvironment in upper tract urothelial carcinoma (UTUC) is unclear. We investigated the clinical significance of relationship between the tumor immune microenvironment and the characteristic oncogene mutations in patients with UTUC using multiplex fluorescent immunohistochemistry.
Methods
We evaluated tumor specimens from 32 patients who underwent nephroureterectomy for UTUC and oncogene mutation analysis. The patients were divided into two groups: with or without neoadjuvant chemotherapy (NAC). The density of each immune cell phenotype, including CD4+ cells, CD8+ cells, CD4+Foxp3+ cells , and CD204+ cells were assessed in the intra-tumoral and peri-tumoral areas between tumor protein (TP) 53, fibroblast growth factor receptor (FGFR) 3, and RAS mutations via multiplex fluorescent immunohistochemistry.
Results
Seven patients (22%) received NAC. Genetic mutation analysis revealed TP53, FGFR3, and RAS mutations in nine (29%), 10 (31%), and 11 patients (34%), respectively. Patients with TP53 mutations showed a significantly higher density of intra-tumoral CD4+Foxp3+ cell (p = 0.0138) and tend toward a higher density of intra-tumoral CD4+ and CD8+ cell compared without TP53 mutations. Focusing for NAC group, the density of intra-tumoral CD4+ cells were significantly higher than non-NAC group (p = 0.0282). Patients with RAS mutations showed no significant difference between NAC and non-NAC group. On the other hand, patients with FGFR3 mutations showed a lower density of each immune cell as a cold tumor compared with other mutations, with or without NAC.
Conclusions
Patients with TP53 mutations showed a higher tumor infiltrating lymphocytes in NAC group, and patients with FGFR3 mutations had fewer immune cells regardless of NAC, suggesting that influences the therapeutic effect of immune checkpoint inhibitors as adjuvant therapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
S. Kitano: Financial Interests, Personal, Advisory Board, Scientific Advisor: ImmuniT Research, United Immunity, Sumitomo Pharma; Financial Interests, Personal, Advisory Board, Scientific advisor: Rakuten Medical; Financial Interests, Personal, Other, lecture fee: AstraZeneca; Financial Interests, Personal, Other, Lecture fee: Pfizer, Taiho, Novartis, MSD, Eisai, Bristol Myers Squibb, GSK, Chugai, Takeda, Janssen, Merck KGaA; Financial Interests, Personal, Other, Scientific adviser, Lecture fee: Ono Pharmaceutical Co., Ltd.; Financial Interests, Personal, Advisory Board: PMDA(Pharmaceuticals and Medical Devices Agency); Financial Interests, Personal and Institutional, Local PI, Clinical Trial, Resarch Grant: Daiichi Sankyo; Financial Interests, Personal and Institutional, Local PI, Clinical Trial: AstraZeneca, Pfizer, MSD, Eisai, Incyte, Takeda, Eli Lilly Japan K.K., Loxo Oncology, AbbVie; Financial Interests, Personal and Institutional, Local PI, Clinical trial, Research Grant: Nippon Boehringer Ingelheim; Financial Interests, Personal and Institutional, Local PI, Cliincal trial: Astellas; Financial Interests, Personal and Institutional, Coordinating PI, Clinical trial, Research Grant: Ono Pharmaceutical Co., Ltd.; Financial Interests, Personal and Institutional, Local PI, Clinical trial: GSK; Financial Interests, Personal and Institutional, Local PI, Clinical Trial, Research Grant: Chugai; Financial Interests, Personal and Institutional, Research Grant, Research Grant: Takara Bio Inc. All other authors have declared no conflicts of interest.