PD-1 blockade and CDK4/6 inhibition augment nonoverlapping features of T cell activation in cancer

被引：20

作者：

Ali, Lestat R. ^{[1
,3
]}

Garrido-Castro, Ana C. ^{[2
,4
]}

Lenehan, Patrick J. ^{[1
,3
]}

Bollenrucher, Naima ^{[1
]}

Stump, Courtney T. ^{[1
,5
]}

Dougan, Michael ^{[4
,5
]}

Goel, Shom ^{[6
,7
]}

Shapiro, Geoffrey I. ^{[2
,4
]}

Tolaney, Sara M. ^{[2
,4
]}

Dougan, Stephanie K. ^{[1
,3
]}

机构：

[1] Dana Farber Canc Inst, Dept Canc Immunol & Virol, Boston, MA 02215 USA

[2] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA

[3] Harvard Med Sch, Dept Immunol, Boston, MA 02215 USA

[4] Harvard Med Sch, Dept Med, Boston, MA USA

[5] Massachusetts Gen Hosp, Dept Med, Div Gastroenterol, Boston, MA USA

[6] Peter MacCallum Canc Ctr, Melbourne, Australia

[7] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Australia

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2023年 / 220卷 / 04期

关键词：

MEMORY; DIFFERENTIATION; PATHWAYS; IMMUNITY;

D O I：

10.1084/jem.20220729

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The authors use single-cell RNA-sequencing and TCR tracking to analyze blood and tumors from breast and ovarian cancer patients treated with PD-1 blockade and CDK4/6 inhibition. They find that both therapies are immunologically active and enhance T cell effector function and memory, respectively. We performed single-cell RNA-sequencing and T cell receptor clonotype tracking of breast and ovarian cancer patients treated with the CDK4/6 inhibitor ribociclib and PD-1 blockade. We highlight evidence of two orthogonal treatment-associated phenomena: expansion of T cell effector populations and promotion of T cell memory formation. Augmentation of the antitumor memory pool by ribociclib boosts the efficacy of subsequent PD-1 blockade in mouse models of melanoma and breast cancer, pointing toward sequential therapy as a potentially safe and synergistic strategy in patients.

引用

页数：16

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