Intratumoral injection of activated B lymphoblast in combination with PD-1 blockade induces systemic antitumor immunity with reduction of local and distal tumors

In spite of the success of PD-1 blocking antibodies in the clinic their benefits are still restricted to a small fraction of patients. Immune-desert tumors and/or the highly immunosuppressive tumor milieu might hamper the success of PD-1/PD-L1 blocking therapies into a broader range of cancer patien...

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Main Authors: Mario M Soldevilla, Helena Villanueva, Naiara Martinez-Velez, Daniel Meraviglia-Crivelli, Marta M Alonso, Javier Cebollero, Ashwathi P Menon, Montserrat Puigdelloses, Fernando Pastor
Format: Article
Language:English
Published: Taylor & Francis Group 2018-08-01
Series:OncoImmunology
Subjects:
pd1
Online Access:http://dx.doi.org/10.1080/2162402X.2018.1450711
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spelling doaj-a00e6e238c7a4f1aa23b2515f56475ec2020-11-25T03:18:50ZengTaylor & Francis GroupOncoImmunology2162-402X2018-08-017810.1080/2162402X.2018.14507111450711Intratumoral injection of activated B lymphoblast in combination with PD-1 blockade induces systemic antitumor immunity with reduction of local and distal tumorsMario M Soldevilla0Helena Villanueva1Naiara Martinez-Velez2Daniel Meraviglia-Crivelli3Marta M Alonso4Javier Cebollero5Ashwathi P Menon6Montserrat Puigdelloses7Fernando Pastor8Molecular Therapeutics Program, Center for Applied Medical Research, CIMA, University of NavarraMolecular Therapeutics Program, Center for Applied Medical Research, CIMA, University of NavarraInstituto de Investigación Sanitaria de Navarra (IDISNA), Recinto de Complejo Hospitalario de NavarraMolecular Therapeutics Program, Center for Applied Medical Research, CIMA, University of NavarraInstituto de Investigación Sanitaria de Navarra (IDISNA), Recinto de Complejo Hospitalario de NavarraMolecular Therapeutics Program, Center for Applied Medical Research, CIMA, University of NavarraMolecular Therapeutics Program, Center for Applied Medical Research, CIMA, University of NavarraInstituto de Investigación Sanitaria de Navarra (IDISNA), Recinto de Complejo Hospitalario de NavarraMolecular Therapeutics Program, Center for Applied Medical Research, CIMA, University of NavarraIn spite of the success of PD-1 blocking antibodies in the clinic their benefits are still restricted to a small fraction of patients. Immune-desert tumors and/or the highly immunosuppressive tumor milieu might hamper the success of PD-1/PD-L1 blocking therapies into a broader range of cancer patients. Although still under debate, there is a cumulative body of evidence that indicates B tumor-infiltrating lymphocytes are a good prognostic marker in most types of cancer, especially in those that form ectopic lymphoid tissue structures. Taking this into account, we reason that the adoptive transfer of activated B lymphoblasts (ABL) in the tumor could be a feasible therapeutic approach to shift the immunosuppressive tumor microenvironment into an immune-permissive one. In this work we show the antitumor effect of ABL therapy in two different tumor models: colon carcinoma (CT26) and melanoma (B16/F10). The ABL transfer in the most relevant non-immunogenic B16/F10 melanoma model depicts synergism with anti-PD-1 antibody therapy. Furthermore, systemic antitumor immunity was detected in mice treated with PD-1 antibody/ABL combination which was able to reach distal metastatic lesions.http://dx.doi.org/10.1080/2162402X.2018.1450711cancer immunotherapyb lymphocytespd1
collection DOAJ
language English
format Article
sources DOAJ
author Mario M Soldevilla
Helena Villanueva
Naiara Martinez-Velez
Daniel Meraviglia-Crivelli
Marta M Alonso
Javier Cebollero
Ashwathi P Menon
Montserrat Puigdelloses
Fernando Pastor
spellingShingle Mario M Soldevilla
Helena Villanueva
Naiara Martinez-Velez
Daniel Meraviglia-Crivelli
Marta M Alonso
Javier Cebollero
Ashwathi P Menon
Montserrat Puigdelloses
Fernando Pastor
Intratumoral injection of activated B lymphoblast in combination with PD-1 blockade induces systemic antitumor immunity with reduction of local and distal tumors
OncoImmunology
cancer immunotherapy
b lymphocytes
pd1
author_facet Mario M Soldevilla
Helena Villanueva
Naiara Martinez-Velez
Daniel Meraviglia-Crivelli
Marta M Alonso
Javier Cebollero
Ashwathi P Menon
Montserrat Puigdelloses
Fernando Pastor
author_sort Mario M Soldevilla
title Intratumoral injection of activated B lymphoblast in combination with PD-1 blockade induces systemic antitumor immunity with reduction of local and distal tumors
title_short Intratumoral injection of activated B lymphoblast in combination with PD-1 blockade induces systemic antitumor immunity with reduction of local and distal tumors
title_full Intratumoral injection of activated B lymphoblast in combination with PD-1 blockade induces systemic antitumor immunity with reduction of local and distal tumors
title_fullStr Intratumoral injection of activated B lymphoblast in combination with PD-1 blockade induces systemic antitumor immunity with reduction of local and distal tumors
title_full_unstemmed Intratumoral injection of activated B lymphoblast in combination with PD-1 blockade induces systemic antitumor immunity with reduction of local and distal tumors
title_sort intratumoral injection of activated b lymphoblast in combination with pd-1 blockade induces systemic antitumor immunity with reduction of local and distal tumors
publisher Taylor & Francis Group
series OncoImmunology
issn 2162-402X
publishDate 2018-08-01
description In spite of the success of PD-1 blocking antibodies in the clinic their benefits are still restricted to a small fraction of patients. Immune-desert tumors and/or the highly immunosuppressive tumor milieu might hamper the success of PD-1/PD-L1 blocking therapies into a broader range of cancer patients. Although still under debate, there is a cumulative body of evidence that indicates B tumor-infiltrating lymphocytes are a good prognostic marker in most types of cancer, especially in those that form ectopic lymphoid tissue structures. Taking this into account, we reason that the adoptive transfer of activated B lymphoblasts (ABL) in the tumor could be a feasible therapeutic approach to shift the immunosuppressive tumor microenvironment into an immune-permissive one. In this work we show the antitumor effect of ABL therapy in two different tumor models: colon carcinoma (CT26) and melanoma (B16/F10). The ABL transfer in the most relevant non-immunogenic B16/F10 melanoma model depicts synergism with anti-PD-1 antibody therapy. Furthermore, systemic antitumor immunity was detected in mice treated with PD-1 antibody/ABL combination which was able to reach distal metastatic lesions.
topic cancer immunotherapy
b lymphocytes
pd1
url http://dx.doi.org/10.1080/2162402X.2018.1450711
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