Nodal immune flare mimics nodal disease progression following neoadjuvant immune checkpoint inhibitors in non-small cell lung cancer

被引：77

作者：

Cascone, Tina ^{[1
]}

Weissferdt, Annikka ^{[2
,3
]}

Godoy, Myrna C. B. ^{[4
]}

William, William N., Jr. ^{[1
,5
]}

Leung, Cheuk H. ^{[6
]}

Lin, Heather Y. ^{[6
]}

Basu, Sreashi ^{[7
]}

Yadav, Shalini S. ^{[7
]}

Pataer, Apar ^{[3
]}

Mitchell, Kyle G. ^{[3
]}

Khan, Md Abdul Wadud ^{[8
]}

Shi, Yushu ^{[6
,9
]}

Haymaker, Cara ^{[10
]}

Solis, Luisa M. ^{[10
]}

Parra, Edwin R. ^{[10
]}

Kadara, Huam ^{[10
]}

Wistuba, Ignacio I. ^{[1
,10
]}

Sharma, Padmanee ^{[7
,11
]}

Allison, James P. ^{[7
,12
]}

Ajami, Nadim J. ^{[13
]}

Wargo, Jennifer A. ^{[8
]}

Jenq, Robert R. ^{[13
,14
]}

Gibbons, Don L. ^{[1
]}

Lee, J. Jack ^{[6
]}

Swisher, Stephen G. ^{[3
]}

Vaporciyan, Araa ^{[3
]}

Heymach, John, V ^{[1
]}

Sepesi, Boris ^{[3
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX USA

[3] Univ Texas MD Anderson Canc Ctr, Dept Thorac & Cardiovasc Surg, Houston, TX USA

[4] Univ Texas MD Anderson Canc Ctr, Dept Thorac Imaging, Houston, TX 77030 USA

[5] Hosp BP, Sao Paulo, Brazil

[6] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX USA

[7] Univ Texas MD Anderson Canc Ctr, Immunotherapy Platform, Houston, TX 77030 USA

[8] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX USA

[9] Univ Missouri, Dept Stat, Columbia, MO 65211 USA

[10] Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA

[11] Univ Texas MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Houston, TX 77030 USA

[12] Univ Texas MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA

[13] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA

[14] Canc Prevent & Res Inst Texas Scholar Canc Res, Houston, TX USA

来源：

NATURE COMMUNICATIONS | 2021年 / 12卷 / 01期

基金：

美国国家卫生研究院;

关键词：

MEDIASTINAL LYMPH-NODES; RESPONSE CRITERIA; PSEUDOPROGRESSION; CHEMOTHERAPY; MICROBIOME; PET;

D O I：

10.1038/s41467-021-25188-0

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Granulomatous/sarcoid-like lesions have been reported in patients treated with immune checkpoint inhibitors (ICIs). Here the authors report the occurrence of "nodal immune flare", an apparent radiological cancer progression in the nodes characterized by the absence of cancer and the presence of non-caseating granulomas, in patients with non-small cell lung cancer following neoadjuvant ICI treatment. Radiographic imaging is the standard approach for evaluating the disease involvement of lymph nodes in patients with operable NSCLC although the impact of neoadjuvant immune checkpoint inhibitors (ICIs) on lymph nodes has not yet been characterized. Herein, we present an ad hoc analysis of the NEOSTAR trial (NCT03158129) where we observed a phenomenon we refer to as "nodal immune flare" (NIF) in which patients treated with neoadjuvant ICIs demonstrate radiologically abnormal nodes post-therapy that upon pathological evaluation are devoid of cancer and demonstrate de novo non-caseating granulomas. Abnormal lymph nodes are analyzed by computed tomography and F-18-fluorodeoxyglucose positron emission tomography/computer tomography to evaluate the size and the maximum standard uptake value post- and pre-therapy in NEOSTAR and an independent neoadjuvant chemotherapy cohort. NIF occurs in 16% (7/44) of patients treated with ICIs but in 0% (0/28) of patients after neoadjuvant chemotherapy. NIF is associated with an inflamed nodal immune microenvironment and with fecal abundance of genera belonging to the family Coriobacteriaceae of phylum Actinobacteria, but not with tumor responses or treatment-related toxicity. Our findings suggest that this apparent radiological cancer progression in lymph nodes may occur due to an inflammatory response after neoadjuvant immunotherapy, and such cases should be evaluated by pathological examination to distinguish NIF from true nodal progression and to ensure appropriate clinical treatment planning.

引用

页数：15

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