RESUMO
Improved identification of anti-tumor T cells is needed to advance cancer immunotherapies. CD39 expression is a promising surrogate of tumor-reactive CD8+ T cells. Here, we comprehensively profiled CD39 expression in human lung cancer. CD39 expression enriched for CD8+ T cells with features of exhaustion, tumor reactivity, and clonal expansion. Flow cytometry of 440 lung cancer biospecimens revealed weak association between CD39+ CD8+ T cells and tumoral features, such as programmed death-ligand 1 (PD-L1), tumor mutation burden, and driver mutations. Immune checkpoint blockade (ICB), but not cytotoxic chemotherapy, increased intratumoral CD39+ CD8+ T cells. Higher baseline frequency of CD39+ CD8+ T cells conferred improved clinical outcomes from ICB therapy. Furthermore, a gene signature of CD39+ CD8+ T cells predicted benefit from ICB, but not chemotherapy, in a phase III clinical trial of non-small cell lung cancer. These findings highlight CD39 as a proxy of tumor-reactive CD8+ T cells in human lung cancer.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Inibidores de Checkpoint Imunológico/uso terapêutico , Linfócitos T CD8-Positivos , ImunoterapiaRESUMO
OBJECTIVES: Up to 70% of women service members in the United States report military sexual trauma (MST); many develop post-traumatic stress disorder (PTSD) and co-occurring disorders. Trauma-informed yoga (TIY) is suggested to improve psychiatric symptoms and shown feasible and acceptable in emerging research, yet no work has evaluated TIY in MST survivors. The current quality improvement project aimed to examine TIY's feasibility, acceptability, and perceived effects in the context of MST. DESIGN: Collective case series (N = 7). SETTING: New England Vet Center. INTERVENTIONS: Extant TIY program (Mindful Yoga Therapy) adapted for Veteran women with MST in concurrent psychotherapy. MAIN OUTCOME MEASURES: Attrition and attendance; qualitative exit interview; validated self-report measure of negative affect pre/post each yoga class, and symptom severity assessments and surveys before (T1; Time 1) and after the yoga program (T2; Time 2). RESULTS: Feasibility was demonstrated and women reported TIY was acceptable. In qualitative interviews, women reported improved symptom severity, diet, exercise, alcohol use, sleep, and pain; reduced medication use; and themes related to stress reduction, mindfulness, and self-compassion. Regarding quantitative change, results suggest acute reductions in negative affect following yoga sessions across participants, as well as improved affect dysregulation, shame, and mindfulness T1 to T2. CONCLUSIONS: TIY is both feasible and acceptable to Veteran women MST survivors in one specific Vet Center, with perceived behavioral health benefits. Results suggest TIY may target psychosocial mechanisms implicated in health behavior change (stress reduction, mindfulness, affect regulation, shame). Formal research should be conducted to confirm these QI project results.