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Acquired cancer cell resistance to T cell bispecific antibodies and CAR T targeting HER2 through JAK2 down-modulation

Several mechanisms of resistance to T cell-engaging therapies have been described for solid tumors. Here, by using T cell bispecific antibodies and chimeric antigen receptors (CAR) T cells targeting HER2, the authors show that cancer cell intrinsic disruption of interferon-gamma signalling, including downregulation of JAK2, confers resistance to T-cell mediated cytotoxicity.

Enrique J. Arenas
Alex Martínez-Sabadell
Joaquín Arribas
ResearchOpen Access23 Feb 2021
Nature Communications

Volume: 12, P: 1-13
Unlocking the potential of engineered immune cell therapy for solid tumors

Adoptive cell therapy has emerged as a promising approach for treating advanced solid malignancies. Genetic engineering techniques represent an exciting area of research for the development of cellular products with enhanced cytotoxicity, phenotype, and metabolism.

Víctor Albarrán-Fernández
Laura Angelats
Aleix Prat
Comments & OpinionOpen Access29 Jan 2025
Nature Communications

Volume: 16, P: 1-5
The efficacy of chemotherapy is limited by intratumoral senescent cells expressing PD-L2

Chaib et al. find that therapy-induced senescent cells have high programmed cell death 1 ligand 2 (PD-L2), contributing to recurrence. They show that PD-L2 blocking combined with chemotherapy is therapeutically beneficial because it reduces senescent cells and immunosuppressive cell recruitment.

Selim Chaib
José Alberto López-Domínguez
Manuel Serrano
ResearchOpen Access24 Jan 2024
Nature Cancer

Volume: 5, P: 448-462
Neoantigen-targeted CD8⁺ T cell responses with PD-1 blockade therapy

Effective anti-PD-1 immunotherapy is associated with the presence of polyclonal CD8⁺ T cells in the tumour and blood specific for a limited number of immunodominant mutations, which are recurrently recognized over time.

Cristina Puig-Saus
Barbara Sennino
Antoni Ribas
Research08 Mar 2023
Nature

Volume: 615, P: 697-704
A machine learning model for ranking candidate HLA class I neoantigens based on known neoepitopes from multiple human tumor types

Robbins and colleagues develop and test a machine learning neoantigen ranking model using experimentally validated neoantigens from human tumors, providing a resource of targetable neoantigens for future immunotherapies.

Jared J. Gartner
Maria R. Parkhurst
Paul F. Robbins
Research03 May 2021
Nature Cancer

Volume: 2, P: 563-574
Ionic immune suppression within the tumour microenvironment limits T cell effector function

Potassium ions released by necrotic cells in tumours impair T cell function by increasing the intracellular potassium concentration in vitro and in vivo.

Robert Eil
Suman K. Vodnala
Nicholas P. Restifo
Research14 Sept 2016
Nature

Volume: 537, P: 539-543
Prospective identification of neoantigen-specific lymphocytes in the peripheral blood of melanoma patients

Steven Rosenberg and colleagues report that PD-1 is a biomarker of CD8⁺ T cells in the blood that recognize mutated neoantigens in melanoma.

Alena Gros
Maria R Parkhurst
Steven A Rosenberg
Research22 Feb 2016
Nature Medicine

Volume: 22, P: 433-438

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Acquired cancer cell resistance to T cell bispecific antibodies and CAR T targeting HER2 through JAK2 down-modulation

Unlocking the potential of engineered immune cell therapy for solid tumors

The efficacy of chemotherapy is limited by intratumoral senescent cells expressing PD-L2

Neoantigen-targeted CD8+ T cell responses with PD-1 blockade therapy

A machine learning model for ranking candidate HLA class I neoantigens based on known neoepitopes from multiple human tumor types

Ionic immune suppression within the tumour microenvironment limits T cell effector function

Prospective identification of neoantigen-specific lymphocytes in the peripheral blood of melanoma patients

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Neoantigen-targeted CD8⁺ T cell responses with PD-1 blockade therapy