1 SUPPLEMENTARY DATA 2 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 1 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. 6 7 2 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) — — — 3 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. 10 4 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 5 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 6 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. 18 7 .