What We're Reading
In the Spotlight
Rising Stars in Cancer Immunology
Targeting multiple inhibitory checkpoints of NK-cell effector function, CIS and TGFβ, unveils new combinatorial NK cell–based immunotherapy that might have broad therapeutic interventions, particularly in settings of NK cell–adoptive cell therapy.
Regulatory Programs of B-cell Activation and Germinal Center Reaction Allow B-ALL Escape from CD19 CAR T-cell Therapy
The authors show CD19-expressing B-ALL cells can employ regulatory programs of normal B-cell activation and germinal center reaction to transcriptionally downregulate and maintain lower CD19 expression, allowing for enhanced survival in the early phases of CAR T-cell exposure.
Design and Validation of Inducible TurboCARs with Tunable Induction and Combinatorial Cytokine Signaling
Inducible Turbo (iTurbo) CAR T cells engineered to express homodimeric chimeric cytokine receptors are demonstrated to exhibit potent antitumor efficacy. Data highlight the flexibility and user-programmable nature of the iTurbo CAR T-cell platform to improve tumor control.
A radiolabeled CD69-directed antibody, [89Zr]-DFO-H1.2F3, combined with PET imaging, shows promise as a noninvasive method to assess early response to immune checkpoint blockade in vivo, with increased uptake in the tumors and lymphoid tissue of blockade-responsive tumor-bearing mice.
Long Noncoding RNA MIR4435-2HG Suppresses Colorectal Cancer Initiation and Progression By Reprogramming Neutrophils
Long noncoding (lnc) RNA MIR4435-2HG can regulate neutrophils/PMN-MDSCs in colorectal cancer (CRC). Data identify this lncRNA as a tumor suppressor in the tumor stroma, rather than as an oncogene in tumor cells, highlighting a potential therapeutic target in CRC.
CD8+ T-cell Responses Are Boosted by Dual PD-1/VEGFR2 Blockade after EGFR Inhibition in Egfr-Mutant Lung Cancer
Egfr-mutant lung cancer exhibits a noninflamed tumor microenvironment (TME). Here, data demonstrate that the scheduling of EGFR inhibition with dual PD-1/VEGFR2 blockade is vital for optimum efficacy and induction of CD8+ T cell–dominant responses in the TME.
The factors that increase tumor-cell chemotactic potential to allow T-cell infiltration remain unclear. The authors find that ADAR1 induction as a result of T-cell/melanoma interactions facilitates tumor infiltration by T cells and may alter response to immunotherapy.
Sensory Nerves Impede the Formation of Tertiary Lymphoid Structures and Development of Protective Antimelanoma Immune Responses
Sensory neurons are shown to play a critical role in the modulation of antitumor immune responses and the formation of tertiary lymphoid structures in melanoma. Data highlight afferent innervation as a potential novel target for cancer immunotherapy.