Abstract 426P
Background
Salivary gland cancer (SGC) is a rare malignancy, and standard chemotherapy for recurrent or metastatic SGC has not been established. In particular, immune checkpoint inhibitors (ICIs) have shown only limited efficacy. However, antibody-drug conjugates (ADCs) have shown promise in other malignancies and have been reported to activate cancer immunity through immunogenic cell death (ICD). Sufficient target protein expression of ADCs is suggested to induce ICD. Here, to explore the potential therapeutic application of ADCs and their combination with ICIs, we investigated the expression of Trop-2 and Nectin-4, and its relationship with the tumor immune microenvironment (TIME).
Methods
We selected five typical pathological types of SGC and evaluated Trop-2 and Nectin-4 expression and TIME. Expression was evaluated by IHC and measured by H-score. TIME was evaluated by multiplexed fluorescent IHC, including CD3, CD8, CD204, Foxp3, and PD-L1.
Results
Trop-2, Nectin-4, and TIME were evaluated in 35 samples. Median H-score of Trop-2 and Nectin-4 was 87.79 (7.82-157.97) and 5.98 (0.18-98.75), respectively. No differences in expression level were seen among pathological types. On further exploration of the relationship between Trop-2 expression and TIME, weak positive correlations were observed with CD3+CD8+ T cells in tumor (r=0.29) and PD-L1 (r=0.30). Conversely, Trop-2 showed a weak negative correlation with CD204+ cells in tumor (r=-0.29). However, no correlation was observed with CD3+CD4+Foxp3+ T cells in tumor (r=0.16). A similar trend was observed for Nectin-4.
Conclusions
Expression level of Trop-2 was reasonably high, suggesting the potential application of Trop-2-directed ADC for SGC. In contrast, expression level of Nectin-4 was low. Additionally, a weak but noticeable correlation was seen between Trop-2 and intra-tumoral CD8-positive cells and PD-L1 expression. Therefore, combination of Trop-2-directed ADC with PD-1/PD-L1 antibodies may be an effective strategy for SGC, and evaluation of this combination in clinical trials is warranted.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Grant-in-Aid for Scientific Research C (Grant number: 17K11384) from the Ministry of Education, Culture, Sports, Science and Technology, Japan.
Disclosure
Y. Nagatani: Financial Interests, Personal, Invited Speaker: Ono, BMS, Daiichi Sankyo, Chugai. N. Kiyota: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical, Bristol Meyers Squibb, Bayer, MSD, Eisai, Lilly, Novartis, Meck Biopharma; Financial Interests, Institutional, Local PI: Ono Pharmaceutical, AstraZeneca, Rakuten Medical, Roche, Bayer, Boehringer Ingelheim, Lilly, AbbVie, GSK; Financial Interests, Institutional, Steering Committee Member: Adlai Nortye. Y. Imamura: Financial Interests, Personal, Invited Speaker: Daiichi Sankyo, MSD, Lilly. T. Koyama: Financial Interests, Personal, Invited Speaker: Shionogi, Merck. K. Sakai: Financial Interests, Personal, Invited Speaker: Qiagen, Inc., Takeda Pharmaceutical Co., Ltd., Nippon Kayaku Co.,Ltd. K. Nishio: Financial Interests, Personal, Invited Speaker: AstraZeneca K.K., Chugai Pharmaceutical CO.,LTD., Novartis Pharma K.K., MSD K.K., Ono Pharmaceutical CO., LTD., Eli Lilly Japan K.K., Daiichi Sankyo, Invitae Japan, Nichirei Biosciences Inc., Maruho Co., Ltd.; Financial Interests, Personal, Advisory Board: Otsuka Pharmaceutical Co., Ltd., SymBio Pharmaceuticals Limited., Guardant Health Inc., Janssen Pharmaceutical; Financial Interests, Personal, Research Grant: West Japan Oncology Group, Nichirei Biosciences Inc., Hitachi, Ltd., osakaminami hospital, Sysmex Corporation, Otsuka Pharmaceutical, Thoracic Oncology Research Group, University Public Corporation Osaka. 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. H. Minami: Financial Interests, Personal, Invited Speaker: Bayer, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Kyowa-Kirin, Ono Pharmaceutical, Ohtsuka, Pfizer, Takeda, AbbVie, Taiho, Lilly, Novartis, Asahai-Kasei, Meiji Seika Pharma; Financial Interests, Institutional, Research Grant: Dainihon Sumitomo, Eisai, Kyowa-Kirin, Nihon Shinyaku, Takeda, Nihon Kayaku, Shionogi, Taiho, Lilly, Chugai Pharma, Daiichi Sankyo, Teijin Pharma, Bayer, Ohtsuka, Asahi Kasei Pharma, Sumitomo Pharma. All other authors have declared no conflicts of interest.