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nature research | reporting summary

October 2018

Validation All antibodies are commercially available and validated by the manufactures for the applications and species used in this study.

See manufactures websites for validation statements (www.abcam.com; http://www.cellsignal.com; https://www.bdbiosciences.com/

en-us; https://www.biolegend.com; https://bxcell.com; https://www.thermofisher.com; https://www.sigmaaldrich.com; https://

http://www.rndsystems.com)

Eukaryotic cell lines

Policy information about cell lines

Cell line source(s) Lewis lung carcinoma cells (LLC1) and 4T1 cells were obtained from ATCC.HNM007, a p53-null murine esophageal squamous

cell carcinoma cell line transformed by HRASG12V, was kindly provided by Prof. S Singhal (University of Pennsylvania).

Authentication No method authentication was performed for the mouse cell lines used.

Mycoplasma contamination Cell lines were routinely tested for mycoplasma and immediately tested upon suspicion. None of the lines used in the

reported experiments tested positive.

Commonly misidentified lines

(See ICLAC register)

None were misidentified.

Animals and other organisms

Policy information about studies involving animals; ARRIVE guidelines recommended for reporting animal research

Laboratory animals 6-8 week-old female C57BL/6 mice and BALB/c mice were purchased from Charles River Laboratories (Wilmington, MA). 6-8

week-old female NOD/SCID/g-chain knockout (NSG) mice, bred and housed at the Johns Hopkins Animal Care Facility, were used.

6-8 week-old female B6.129S4-Ccr2tm1Ifc/J mice were kindly provided by Prof. Sharon A. McGrath-Morrow (Johns Hopkins

University). 6-8 week-old female mice congenic in murine CD45 at the Ly5 locus (B.6SJL-Ptprca Pepcb/BoyJ Ly5.1) were obtained

from Jackson Laboratory.

Wild animals No wild animals were used in the study.

Field-collected samples No field-collected samples were used in the study.

Ethics oversight The Guide for the Care and Use of Laboratory Animals published by the National Institutes of Health (NIH publication 96-01,

revised 1996) were followed, and all protocols were approved by the Johns Hopkins University Animal Care and Use Committee.

Note that full information on the approval of the study protocol must also be provided in the manuscript.

Human research participants

Policy information about studies involving human research participants

Population characteristics 13 patients(4 female, 9 male) with stage I non-small cell lung cancer and an Eastern Cooperative Oncology Group (ECOG)

performance status of 0-1 after curative surgery.

Recruitment Patients with stage I NSCLC who presented at John Hopkins for medical care and fulfilled the eligibility criteria as per approved

protocol were offered participation in the study. We are unaware of any potential self-selection bias or other biases present.

Ethics oversight Human biological samples were sourced ethically and their research use was in accord with the terms of the informed consent

provided under the institutional protocols approved either by Johns Hopkins Hospital Ethics Committee.

Note that full information on the approval of the study protocol must also be provided in the manuscript.

Clinical data

Policy information about clinical studies
All manuscripts should comply with the ICMJE guidelines for publication of clinical research and a completed CONSORT checklist must be included with all submissions.

Clinical trial registration NCT01207726

Study protocol Study protocol is accessible on Clinical Trials website. More information is available from the corresponding author upon

reasonable request.

Data collection The J1037 (NCT01207726) study was a randomized phase II study that compared the low dose adjuvant epigenetic therapy (Aza

plus entinostat) with standard of care (observation) in patients with stage I (T1-2aN0) NSCLC after primary tumour resection in

Johns Hopkins Hospital and Anne Anmdel Medical Center. The patients from the adjuvant epigenetic treatment group received

the combination of azacitidine at 40 mg/m2 on days 1-5 and 8-10 with entinostat at a 7 mg fixed dose on days 3 and 10 of each

28 days cycle. The primary end point was the effect of Aza plus entinostat on the hazard of 3 years progression-free survival in

patients with resected stage I non-small cell lung cancer. Finally, thirteen patients were enrolled in the trial. Due to the difficulty

in enrolling patients, the trial was prematurely terminated on May 1, 2015.