SUPPLEMENTARY DATA Supplementary Tables Table S1

1 SUPPLEMENTARY DATA

3 Supplementary Tables

4 Table S1. Gene signatures

Gene signature Genes

Cytolytic GNLY, KLRK1, KLRB1, GZMH, GZMA, KLRD1, NKG7

Cytotoxic CD8+ T cells CD8A, GZMA, GZMB, IFNG, EOMES, PRF1

Activated CD4+ T cells CD4, IL2RA, CD69

CD4+ Treg cells FOXP3, CTLA4, ICOS

Immune checkpoints—T cells BTLA, LAG3, HAVCR2, PDCD1, TIGIT, CTLA4

T cells CD2, CD3D, CD3E, CD3G, CD6, TRAT1, CD28, LCK

B cells CD79A, MS4A1, CD19, STAP1, KIAA0125, POU2AF1, FCRL5

NK cells SLAMF7, KLRC3, KLRK1, KLRC2, KLRD1

Monocytes CD14, CD16, CD163, CSF1R, HLA-DR

LAPTM5, LAIR1, CD4, CSF1R, CD163, ADAP2, CD68, MRC1,

M2 macrophages PTPRC, SLA, SEPSECS, MSR1, FPR3, FCGR2A, FCGR3A,

IDO1, RERE, ABL2, CD163L1, STAT3, SBNO2, CSF1, CSF2

FAP, FN1, MMP2, BGN, LOXL2, PDPN, PDGFRB, COL12a1, Active fibroblasts COL5A1, COL8A2, THY1, PALLD

Antigen processing TAPBP, TAP1, TAP2, PSMB9, PSMB8

Immune checkpoints—APC CD274, PDCD1LG2, IDO1

Costimulatory ligands CD40, CD80, CD86, CD70, TNFRSF18

CD27, CD28, ICOS, TNFRSF4, TNFRSF14, TNFRSF18, Costimulatory receptors TNFSF14, CD226

Myeloid inflammation CCL2, IL1B, CXCL8, IL6, PTGS2

DERL1, DERL2, DNAJB11, DNAJB9, DNAJC10, DNAJC3,

ER stress EDEM1, EDEM2, EDEM3, EIF2AK3, ERO1L, HERPUD1,

PDIA3, PDIA6, SEC61A1, SERP1, SYVN1

RRM2, UBE2C, BIRC5, CEP55, CCNB1, NUF2, NDC80, Proliferation MKI67, CDC20, TYMS

5 ER, endoplasmic reticulum; NK, natural killer.

8 Table S2. Most common all-cause and treatment-related AEs

Patients (N = 45)

All cause Treatment related

Eventa Any grade Grade 3/4 Any grade Grade 3/4

Any AE 45 (100.0) 20 (44.4) 35 (77.8) 8 (17.8)

Fatigue 27 (60.0) 1 (2.2) 20 (44.4) 1 (2.2)

Headache 16 (35.6) — 6 (13.3) —

Diarrhea 14 (31.1) 1 (2.2) 5 (11.1) —

Nausea 12 (26.7) — 6 (13.3) —

Cough 12 (26.7) — — —

Decreased appetite 11 (24.4) — 5 (11.1) —

Dyspnea 11 (24.4) — — —

Pruritus 11 (24.4) — 9 (20.0) —

Pyrexia 10 (22.2) — 8 (17.8) —

Back pain 9 (20.0) 2 (4.4) — —

Constipation 9 (20.0) — — —

Rash 9 (20.0) — 8 (17.8) —

Arthralgia 8 (17.8) 1 (2.2) 7 (15.6) —

Insomnia 8 (17.8) — — —

Oropharyngeal pain 8 (17.8) — — —

Upper respiratory tract infection 8 (17.8) — — —

Chills 7 (15.6) — 6 (13.3) —

Hyperglycemia 7 (15.6) 4 (8.9) — —

Musculoskeletal pain 7 (15.6) — — —

Vomiting 7 (15.6) — — —

Flank pain 6 (13.3) 1 (2.2) — —

Nasal congestion 6 (13.3) — — —

Peripheral edema 6 (13.3) — — —

Productive cough 6 (13.3) — — —

Maculopapular rash 6 (13.3) — 5 (11.1) —

Abdominal pain 5 (11.1) — — —

Anemia 5 (11.1) 1 (2.2) — —

Dizziness 5 (11.1) — — —

Dry skin 5 (11.1) — — —

Myalgia 5 (11.1) — — —

Pain 5 (11.1) 1 (2.2) — —

Hyponatremia 4 (8.9) 2 (4.4) — —

Increased ALT 4 (8.9) 2 (4.4) 3 (6.7) 2 (4.4)

9 a Any-grade AEs occurring in ≥ 10% of patients; grade 3/4 AEs occurring in ≥ 2 patients.

11 Table S3. Treatment-related toxicity over time

Patients (N = 45)

≤ 1 year 1-2 years 2-3 years ≥ 3 years

(n = 45) (n = 7) (n = 6) (n = 5)

Any Grade Any Grade Any Grade Any Grade

grade 3/4 grade 3/4 grade 3/4 grade 3/4

Any related AE 35 (77.8) 8 (17.7) 3 (42.9) — 3 (50.0) — 2 (40.0) —

Fatigue 18 (40.0) 1 (2.2) 1 (14.3) — 3 (50.0) — — —

Pruritus 8 (17.8) — 2 (28.6) — — — 1 (20.0) —

Pyrexia 8 (17.8) — 1 (14.3) — — — — —

Arthralgia 7 (15.6) — — — — — — —

Rash 7 (15.6) — 1 (14.3) — — — — —

Chills 6 (13.3) — — — — — — —

Headache 6 (13.3) — — — — — — —

Nausea 6 (13.3) — — — — — — —

Decreased appetite 5 (11.1) — — — — — — —

Diarrhea 5 (11.1) — — — 1 (16.7) — 1 (20.0) —

Maculopapular rash 5 (11.1) — — — — — — —

Increased ALT 3 (6.7) 2 (4.4) — — — — — —

Myalgia 3 (6.7) — 1 (14.3) — — — — —

Influenza-like illness 1 (2.2) — 1 (14.3) — — — — —

Dysphonia — — — — 1 (16.7) — — —

Hemoptysis — — — — 1 (16.7) — — —

Upper respiratory tract — — — — 1 (16.7) — — —

infection

Arthritis — — — — — — 1 (20.0) —

Lymphadenopathy — — — — — — 1 (20.0) —

Perivascular dermatitis — — — — — — 1 (20.0) —

Pruritic rash — — — — — — 1 (20.0) —

12 a Any-grade treatment-related AEs occurring in ≥ 10% of patients; grade 3/4 treatment-related 13 AEs occurring in ≥ 2 patients. 14

15 Table S4. Tumor PD-L1 IHC status

PD-L1 IC n (%) PD-L1 TC n (%)

IC0 (< 1%) 17 (37.8)a TC0 (< 1%) 34 (75.6)

IC1 (≥1% to <5%) 4 (8.9) TC1 (≥ 1% to < 5%) 3 (6.7)

IC2 (≥ 5% to <10%) 3 (6.7) TC2 (≥ 5% to < 50%) 2 (4.4)

IC3 (≥ 10%) 15 (33.3) TC3 (≥ 50%) 0

Unknown 6 (13.3) Unknown 6 (13.3)

16 a One patient received < 1 mg/kg of atezolizumab and was excluded from the efficacy-evaluable

17 population for PD-L1 IC.