Dual CD47 and PD‐L1 blockade elicits anti‐tumor immunity by intratumoral CD8+ T cells
Abstract Objectives Bispecific antibodies targeting CD47 and PD‐L1 (CD47 × PD‐L1 BisAb) demonstrate efficacy against a range of solid cancers. While dual blockade negates anti‐CD47‐mediated toxicity, the effect of combined innate and adaptive immune activation on protective tumor‐resident CD8+ T cel...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-01-01
|
| Series: | Clinical & Translational Immunology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cti2.70014 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846120583284129792 |
|---|---|
| author | Susan N Christo Keely M McDonald Thomas N Burn Nadia Kurd Jessica Stanfield Megan M Kaneda Ruth Seelige Christopher P Dillon Timothy S Fisher Bas Baaten Laura K Mackay |
| author_facet | Susan N Christo Keely M McDonald Thomas N Burn Nadia Kurd Jessica Stanfield Megan M Kaneda Ruth Seelige Christopher P Dillon Timothy S Fisher Bas Baaten Laura K Mackay |
| author_sort | Susan N Christo |
| collection | DOAJ |
| description | Abstract Objectives Bispecific antibodies targeting CD47 and PD‐L1 (CD47 × PD‐L1 BisAb) demonstrate efficacy against a range of solid cancers. While dual blockade negates anti‐CD47‐mediated toxicity, the effect of combined innate and adaptive immune activation on protective tumor‐resident CD8+ T cells has yet to be fully elucidated. Methods CD8+ T cell populations were tracked upon CD47 × PD‐L1 BisAb treatment in an orthotopic model of murine breast cancer where anti‐tumor immunity is mediated by CD8+ T cells. Immune responses were also compared with anti‐PD‐L1 monotherapy to assess the advantage of dual checkpoint targeting. Results We found that CD47 × PD‐L1 BisAb treatment augmented CD8+ T cell responses in tumors, which resulted in enhanced tumor control. Compared with anti‐PD‐L1 treatment, dual CD47 and PD‐L1 blockade promoted greater numbers of antigen‐specific tumor‐resident CD8+ T cells that exhibited increased cytokine production. Conclusions Engagement of innate and adaptive immune checkpoint molecules via CD47 × PD‐L1 BisAb treatment resulted in robust CD8+ T cell responses, including the induction of tumor‐resident CD8+ T cells that exhibited functionally superior anti‐tumor immunity. These results demonstrate that innate immune activation potentiates anti‐tumor adaptive responses, highlighting the use of dual checkpoint blockade as an optimal strategy for promoting CD8+ T cell‐mediated protection. |
| format | Article |
| id | doaj-art-6a8dad7b15e94e2b9af5d8772594ea0f |
| institution | Kabale University |
| issn | 2050-0068 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical & Translational Immunology |
| spelling | doaj-art-6a8dad7b15e94e2b9af5d8772594ea0f2024-12-16T08:11:16ZengWileyClinical & Translational Immunology2050-00682024-01-011311n/an/a10.1002/cti2.70014Dual CD47 and PD‐L1 blockade elicits anti‐tumor immunity by intratumoral CD8+ T cellsSusan N Christo0Keely M McDonald1Thomas N Burn2Nadia Kurd3Jessica Stanfield4Megan M Kaneda5Ruth Seelige6Christopher P Dillon7Timothy S Fisher8Bas Baaten9Laura K Mackay10Department of Microbiology and Immunology The University of Melbourne at the Peter Doherty Institute for Infection and Immunity Melbourne AustraliaDepartment of Microbiology and Immunology The University of Melbourne at the Peter Doherty Institute for Infection and Immunity Melbourne AustraliaDepartment of Microbiology and Immunology The University of Melbourne at the Peter Doherty Institute for Infection and Immunity Melbourne AustraliaOncology Research Unit Pfizer Inc. San Diego CA USAOncology Research Unit Pfizer Inc. San Diego CA USAOncology Research Unit Pfizer Inc. San Diego CA USAOncology Research Unit Pfizer Inc. San Diego CA USAOncology Research Unit Pfizer Inc. San Diego CA USAOncology Research Unit Pfizer Inc. San Diego CA USAOncology Research Unit Pfizer Inc. San Diego CA USADepartment of Microbiology and Immunology The University of Melbourne at the Peter Doherty Institute for Infection and Immunity Melbourne AustraliaAbstract Objectives Bispecific antibodies targeting CD47 and PD‐L1 (CD47 × PD‐L1 BisAb) demonstrate efficacy against a range of solid cancers. While dual blockade negates anti‐CD47‐mediated toxicity, the effect of combined innate and adaptive immune activation on protective tumor‐resident CD8+ T cells has yet to be fully elucidated. Methods CD8+ T cell populations were tracked upon CD47 × PD‐L1 BisAb treatment in an orthotopic model of murine breast cancer where anti‐tumor immunity is mediated by CD8+ T cells. Immune responses were also compared with anti‐PD‐L1 monotherapy to assess the advantage of dual checkpoint targeting. Results We found that CD47 × PD‐L1 BisAb treatment augmented CD8+ T cell responses in tumors, which resulted in enhanced tumor control. Compared with anti‐PD‐L1 treatment, dual CD47 and PD‐L1 blockade promoted greater numbers of antigen‐specific tumor‐resident CD8+ T cells that exhibited increased cytokine production. Conclusions Engagement of innate and adaptive immune checkpoint molecules via CD47 × PD‐L1 BisAb treatment resulted in robust CD8+ T cell responses, including the induction of tumor‐resident CD8+ T cells that exhibited functionally superior anti‐tumor immunity. These results demonstrate that innate immune activation potentiates anti‐tumor adaptive responses, highlighting the use of dual checkpoint blockade as an optimal strategy for promoting CD8+ T cell‐mediated protection.https://doi.org/10.1002/cti2.70014adaptive immunityCD47CD8+ T cellsimmune checkpoint blockadeimmunotherapytumor‐resident CD8+ T cells |
| spellingShingle | Susan N Christo Keely M McDonald Thomas N Burn Nadia Kurd Jessica Stanfield Megan M Kaneda Ruth Seelige Christopher P Dillon Timothy S Fisher Bas Baaten Laura K Mackay Dual CD47 and PD‐L1 blockade elicits anti‐tumor immunity by intratumoral CD8+ T cells Clinical & Translational Immunology adaptive immunity CD47 CD8+ T cells immune checkpoint blockade immunotherapy tumor‐resident CD8+ T cells |
| title | Dual CD47 and PD‐L1 blockade elicits anti‐tumor immunity by intratumoral CD8+ T cells |
| title_full | Dual CD47 and PD‐L1 blockade elicits anti‐tumor immunity by intratumoral CD8+ T cells |
| title_fullStr | Dual CD47 and PD‐L1 blockade elicits anti‐tumor immunity by intratumoral CD8+ T cells |
| title_full_unstemmed | Dual CD47 and PD‐L1 blockade elicits anti‐tumor immunity by intratumoral CD8+ T cells |
| title_short | Dual CD47 and PD‐L1 blockade elicits anti‐tumor immunity by intratumoral CD8+ T cells |
| title_sort | dual cd47 and pd l1 blockade elicits anti tumor immunity by intratumoral cd8 t cells |
| topic | adaptive immunity CD47 CD8+ T cells immune checkpoint blockade immunotherapy tumor‐resident CD8+ T cells |
| url | https://doi.org/10.1002/cti2.70014 |
| work_keys_str_mv | AT susannchristo dualcd47andpdl1blockadeelicitsantitumorimmunitybyintratumoralcd8tcells AT keelymmcdonald dualcd47andpdl1blockadeelicitsantitumorimmunitybyintratumoralcd8tcells AT thomasnburn dualcd47andpdl1blockadeelicitsantitumorimmunitybyintratumoralcd8tcells AT nadiakurd dualcd47andpdl1blockadeelicitsantitumorimmunitybyintratumoralcd8tcells AT jessicastanfield dualcd47andpdl1blockadeelicitsantitumorimmunitybyintratumoralcd8tcells AT meganmkaneda dualcd47andpdl1blockadeelicitsantitumorimmunitybyintratumoralcd8tcells AT ruthseelige dualcd47andpdl1blockadeelicitsantitumorimmunitybyintratumoralcd8tcells AT christopherpdillon dualcd47andpdl1blockadeelicitsantitumorimmunitybyintratumoralcd8tcells AT timothysfisher dualcd47andpdl1blockadeelicitsantitumorimmunitybyintratumoralcd8tcells AT basbaaten dualcd47andpdl1blockadeelicitsantitumorimmunitybyintratumoralcd8tcells AT laurakmackay dualcd47andpdl1blockadeelicitsantitumorimmunitybyintratumoralcd8tcells |