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Conference Paper: Altered expression of immune regulatory receptors upon combination of chemotherapy and checkpoint blockade immunotherapy in a lung cancer mouse model

TitleAltered expression of immune regulatory receptors upon combination of chemotherapy and checkpoint blockade immunotherapy in a lung cancer mouse model
Authors
Issue Date2020
PublisherHong Kong Academy of Medicine Press. The Journal's web site is located at http://www.hkmj.org/
Citation
25th Medical Research Conference 2020, Hong Kong, 18 January 2020. In Hong Kong Medical Journal, 2020, v. 26 n. 1, Suppl. 1, p. 11, asbtract no. 11 How to Cite?
AbstractIntroduction: Lung cancer remains as the most lethal cancer disease in Hong Kong. Although blockade of inhibitory immune checkpoints achieved remarkable clinical outcomes, acquired immune resistance arises as dynamic interactions between the cancer cells and the tumour-associated microenvironment evolve. Exploration on alternative strategies to battle against lung cancer is therefore necessary for long-term tumour suppression. Methods: Murine lung cancer model was established by inoculation of Lewis lung carcinoma cells subcutaneously on the flank of C57BL/6J mice. Chemotherapy (cisplatin or pemetrexed) or antibody to programmed cell death protein 1 (anti-PD-1) alone, or in combination started at 7 days post-inoculation for 2 weeks. Tumour growth was measured by digital calliper and survival rate was recorded. Mice were sacrificed when they reached the humane endpoint. Splenocytes and tumour cells were harvested and expression of immune regulatory markers (including PD-L1, PD-1, Tim-3, OX-40, GITR, LAG-3 and CTLA-4) was analysed by flow cytometry. Results: While PD-1 blockade delayed tumour growth (P<0.001), no significant difference in overall survival was observed. Systemically, anti-PD-1 immunotherapy induced upregulation of Tim-3, OX-40 and GITR; cisplatin ± anti-PD-1 induced upregulation of GITR; whilst OX-40 is induced in both combinations of chemotherapy and anti-PD-1. Tumour-infiltrating T cells were increased in anti-PD-1–treated mice, while combination of pemetrexed and anti-PD-1 induced upregulation of co-stimulatory receptors including GITR and OX-40 within tumour. Conclusion: Cisplatin and pemetrexed induced different systematic and intratumoural immune responses when used alone or in combination with anti-PD-1 treatment. Increased expression of co-stimulatory receptors in the tumour in response to combination therapy provide insights for investigation of synergism on anti-PD-1 and alternative therapeutic targets. Acknowledgement This study was supported by YC Chan Scientist Award 2019 and Donation from Lifestyle International Holdings Limited.
Persistent Identifierhttp://hdl.handle.net/10722/286452
ISSN
2023 Impact Factor: 3.1
2023 SCImago Journal Rankings: 0.261

 

DC FieldValueLanguage
dc.contributor.authorYan, S-
dc.contributor.authorLam, SK-
dc.contributor.authorHo, JCM-
dc.date.accessioned2020-08-31T07:04:04Z-
dc.date.available2020-08-31T07:04:04Z-
dc.date.issued2020-
dc.identifier.citation25th Medical Research Conference 2020, Hong Kong, 18 January 2020. In Hong Kong Medical Journal, 2020, v. 26 n. 1, Suppl. 1, p. 11, asbtract no. 11-
dc.identifier.issn1024-2708-
dc.identifier.urihttp://hdl.handle.net/10722/286452-
dc.description.abstractIntroduction: Lung cancer remains as the most lethal cancer disease in Hong Kong. Although blockade of inhibitory immune checkpoints achieved remarkable clinical outcomes, acquired immune resistance arises as dynamic interactions between the cancer cells and the tumour-associated microenvironment evolve. Exploration on alternative strategies to battle against lung cancer is therefore necessary for long-term tumour suppression. Methods: Murine lung cancer model was established by inoculation of Lewis lung carcinoma cells subcutaneously on the flank of C57BL/6J mice. Chemotherapy (cisplatin or pemetrexed) or antibody to programmed cell death protein 1 (anti-PD-1) alone, or in combination started at 7 days post-inoculation for 2 weeks. Tumour growth was measured by digital calliper and survival rate was recorded. Mice were sacrificed when they reached the humane endpoint. Splenocytes and tumour cells were harvested and expression of immune regulatory markers (including PD-L1, PD-1, Tim-3, OX-40, GITR, LAG-3 and CTLA-4) was analysed by flow cytometry. Results: While PD-1 blockade delayed tumour growth (P<0.001), no significant difference in overall survival was observed. Systemically, anti-PD-1 immunotherapy induced upregulation of Tim-3, OX-40 and GITR; cisplatin ± anti-PD-1 induced upregulation of GITR; whilst OX-40 is induced in both combinations of chemotherapy and anti-PD-1. Tumour-infiltrating T cells were increased in anti-PD-1–treated mice, while combination of pemetrexed and anti-PD-1 induced upregulation of co-stimulatory receptors including GITR and OX-40 within tumour. Conclusion: Cisplatin and pemetrexed induced different systematic and intratumoural immune responses when used alone or in combination with anti-PD-1 treatment. Increased expression of co-stimulatory receptors in the tumour in response to combination therapy provide insights for investigation of synergism on anti-PD-1 and alternative therapeutic targets. Acknowledgement This study was supported by YC Chan Scientist Award 2019 and Donation from Lifestyle International Holdings Limited.-
dc.languageeng-
dc.publisherHong Kong Academy of Medicine Press. The Journal's web site is located at http://www.hkmj.org/-
dc.relation.ispartofHong Kong Medical Journal-
dc.relation.ispartofMedical Research Conference 2020-
dc.rightsHong Kong Medical Journal. Copyright © Hong Kong Academy of Medicine Press.-
dc.titleAltered expression of immune regulatory receptors upon combination of chemotherapy and checkpoint blockade immunotherapy in a lung cancer mouse model-
dc.typeConference_Paper-
dc.identifier.emailYan, S: ssyan@hku.hk-
dc.identifier.emailLam, SK: sklam77@hku.hk-
dc.identifier.emailHo, JCM: jhocm@hku.hk-
dc.identifier.authorityHo, JCM=rp00258-
dc.identifier.hkuros313092-
dc.identifier.volume26-
dc.identifier.issue1, Suppl. 1-
dc.identifier.spage11, asbtract no. 11-
dc.identifier.epage11, asbtract no. 11-
dc.publisher.placeHong Kong-
dc.identifier.issnl1024-2708-

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