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Conference Paper: Study of immune regulatory receptor expression upon combination of chemotherapy and immune checkpoint blockade in a murine lung cancer model
Title | Study of immune regulatory receptor expression upon combination of chemotherapy and immune checkpoint blockade in a murine lung cancer model |
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Authors | |
Keywords | Programmed cell death protein 1 Combination chemotherapy Immune checkpoint antibodies Programmed death ligand 1 Tumor size |
Issue Date | 2020 |
Publisher | American Society of Clinical Oncology. The Journal's web site is located at http://www.jco.org/ |
Citation | 2020 American Society of Clinical Oncology (ASCO) Annual Meeting, Virtual Meeting, Chicago, IL, USA, 29 May - 2 June 2020. In Journal of Clinical Oncology, 2020 , v. 38 n. 15, Suppl., abstract no. e21083 How to Cite? |
Abstract | Background: Blockade of inhibitory immune checkpoints namely the programmed cell death protein 1 (PD-1) and the PD-1 ligand (PD-L1) achieved remarkable clinical outcomes in multiple malignant diseases including lung cancer. However, as the dynamic interactions between the cancer cells and the tumor-associated microenvironment evolves, acquired resistance arises. Thus exploration on alternative strategies would be necessary in order to reach long-term tumor 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 anti-PD-1 alone, or in combination started at 7 days post-inoculation as tumor growth was established. Digital caliper was used to measure tumor sizes and survival rates were recorded. Mice were sacrificed upon humane endpoint (tumor size > 17 mm in diameter). Splenocytes and tumor 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 analyzed by flow cytometry. Results: While PD-1 blockade delayed tumor growth (p< 0.001), there was no significant difference in overall survival. Systemically, anti-PD-1 immunotherapy induced upregulation of Tim-3, OX-40 and GITR; cisplatin alone and in combination with anti-PD-1 induced upregulation of GITR; OX-40 is upregulated in combinations of chemotherapy and anti-PD-1. Population of tumor-infiltrating T cells were increased in anti-PD-1-treated mice, while combination of pemetrexed and anti-PD-1 prompted augmented expression of co-stimulatory receptors including GITR and OX-40 within tumor. Conclusions: Cisplatin and pemetrexed triggered different systematic and intratumoral immune responses when used alone or in combination with anti-PD-1 treatment. Increased expression of co-stimulatory receptors in the tumor in response to combination therapy provide insights for investigation of synergism on anti-PD-1 and alternative therapeutic targets. |
Description | Session: Publication Only: Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers - Abstract # e21083 |
Persistent Identifier | http://hdl.handle.net/10722/286455 |
ISSN | 2023 Impact Factor: 42.1 2023 SCImago Journal Rankings: 10.639 |
DC Field | Value | Language |
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dc.contributor.author | Ho, JCM | - |
dc.contributor.author | Yan, S | - |
dc.contributor.author | Lam, SK | - |
dc.date.accessioned | 2020-08-31T07:04:07Z | - |
dc.date.available | 2020-08-31T07:04:07Z | - |
dc.date.issued | 2020 | - |
dc.identifier.citation | 2020 American Society of Clinical Oncology (ASCO) Annual Meeting, Virtual Meeting, Chicago, IL, USA, 29 May - 2 June 2020. In Journal of Clinical Oncology, 2020 , v. 38 n. 15, Suppl., abstract no. e21083 | - |
dc.identifier.issn | 0732-183X | - |
dc.identifier.uri | http://hdl.handle.net/10722/286455 | - |
dc.description | Session: Publication Only: Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers - Abstract # e21083 | - |
dc.description.abstract | Background: Blockade of inhibitory immune checkpoints namely the programmed cell death protein 1 (PD-1) and the PD-1 ligand (PD-L1) achieved remarkable clinical outcomes in multiple malignant diseases including lung cancer. However, as the dynamic interactions between the cancer cells and the tumor-associated microenvironment evolves, acquired resistance arises. Thus exploration on alternative strategies would be necessary in order to reach long-term tumor 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 anti-PD-1 alone, or in combination started at 7 days post-inoculation as tumor growth was established. Digital caliper was used to measure tumor sizes and survival rates were recorded. Mice were sacrificed upon humane endpoint (tumor size > 17 mm in diameter). Splenocytes and tumor 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 analyzed by flow cytometry. Results: While PD-1 blockade delayed tumor growth (p< 0.001), there was no significant difference in overall survival. Systemically, anti-PD-1 immunotherapy induced upregulation of Tim-3, OX-40 and GITR; cisplatin alone and in combination with anti-PD-1 induced upregulation of GITR; OX-40 is upregulated in combinations of chemotherapy and anti-PD-1. Population of tumor-infiltrating T cells were increased in anti-PD-1-treated mice, while combination of pemetrexed and anti-PD-1 prompted augmented expression of co-stimulatory receptors including GITR and OX-40 within tumor. Conclusions: Cisplatin and pemetrexed triggered different systematic and intratumoral immune responses when used alone or in combination with anti-PD-1 treatment. Increased expression of co-stimulatory receptors in the tumor in response to combination therapy provide insights for investigation of synergism on anti-PD-1 and alternative therapeutic targets. | - |
dc.language | eng | - |
dc.publisher | American Society of Clinical Oncology. The Journal's web site is located at http://www.jco.org/ | - |
dc.relation.ispartof | Journal of Clinical Oncology | - |
dc.relation.ispartof | 2020 American Society of Clinical Oncology (ASCO) Virtual Meeting | - |
dc.subject | Programmed cell death protein 1 | - |
dc.subject | Combination chemotherapy | - |
dc.subject | Immune checkpoint antibodies | - |
dc.subject | Programmed death ligand 1 | - |
dc.subject | Tumor size | - |
dc.title | Study of immune regulatory receptor expression upon combination of chemotherapy and immune checkpoint blockade in a murine lung cancer model | - |
dc.type | Conference_Paper | - |
dc.identifier.email | Ho, JCM: jhocm@hku.hk | - |
dc.identifier.email | Yan, S: ssyan@hku.hk | - |
dc.identifier.email | Lam, SK: sklam77@hku.hk | - |
dc.identifier.authority | Ho, JCM=rp00258 | - |
dc.identifier.doi | 10.1200/JCO.2020.38.15_suppl.e21083 | - |
dc.identifier.hkuros | 313106 | - |
dc.identifier.volume | 38 | - |
dc.identifier.issue | 15, Suppl. | - |
dc.identifier.spage | abstract no. e21083 | - |
dc.identifier.epage | abstract no. e21083 | - |
dc.publisher.place | United States | - |
dc.identifier.issnl | 0732-183X | - |