Real-World Outcomes of Pralsetinib in RET Fusion-Positive NSCLC.

Introduction: Pralsetinib is a RET inhibitor found to have antitumor activity in advanced, metastatic, fusion-positive NSCLC.

Objective: To assess real-world efficacy of pralsetinib and treatment sequences in patients with RET fusion-positive NSCLC.

Design: Retrospective study of consecutive patients enrolled in the French expanded-access program for pralsetinib from December 1, 2019, to December 31, 2021.

Outcomes Analysis of Patients Receiving Local Ablative Therapy for Oligoprogressive Metastatic NSCLC Under First-Line Immunotherapy.

Context: Nonsmall Cell Lung Cancer (NSCLC) treatment relies on first-line immunotherapy as single agent or combined with chemotherapy. Oligoprogression may be observed in this setting.

Material And Method: We performed a European multicentric retrospective study on patients treated with first-line immunotherapy, who presented with oligoprogressive disease, treated with a local ablative treatment.

Divergent local and systemic antitumor response in primary uveal melanomas.

Uveal melanoma (UM) is the most common cancer of the eye. The loss of chromosome 3 (M3) is associated with a high risk of metastases. M3 tumors are more infiltrated by T-lymphocytes than low-risk disomic-3 (D3) tumors, contrasting with other tumor types in which T cell infiltration correlates with better prognosis.

In vivo genome-wide CRISPR screens identify SOCS1 as intrinsic checkpoint of CD4 T1 cell response.

Although CD8 T cells undergo autonomous clonal proliferation after antigen stimulation in vivo, the expansion of activated CD4 T cells is limited by intrinsic factors that are poorly characterized. Using genome-wide CRISPR-Cas9 screens and an in vivo system modeling of antigen-experienced CD4 T cell recruitment and proliferation during a localized immune response, we identified suppressor of cytokine signaling 1 (SOCS1) as a major nonredundant checkpoint imposing a brake on CD4 T cell proliferation. Using anti–interleukin-2 receptor (IL-2R) blocking antibodies, interferon-γ receptor (IFN-γR) knockout mice, and transcriptomic analysis, we show that SOCS1 is a critical node integrating both IL-2 and IFN-γ signals to block multiple downstream signaling pathways abrogating CD4 T helper 1 (T1) cell response.