Supplementary Table 2: Differentially expressed gene list contrasting tumour region of origin between Central Tumor and Invasive Front. Supplementary Table 3: Differentially expressed gene list contrasting tumour region of origin between CT-LN. Supplementary Table 4: Differentially expressed gene list contrasting tumour region of origin between LN-IF.

Figure legends for Supplementary Figures

This Supplementary Figure indicates the project plan

This Supplementary Table indicates the sample source for the study

EphA2 and EFNA1 expression levels in colorectal cancer cells.

Role of p53, Src family kinases and RAS/MAPK pathway in regulating EphA2 expression levels.

The role of microenvironment-derived ligands in regulating EphA2 expression levels.

Response of H460 and A549 cells to IR

Combination of SAHA with IR in H460 and A549 cells using different treatment schedules

Supplementary table 1. Clinical-pathological features of the resection-only and chemotherapy/resection stage II/III colorectal cancer patient cohorts with mature survival data in the Singapore dataset. Supplementary table 2. EphA2 and clinical-pathological correlates in CRC. Correlation between EphA2 and CD44, LGR5, CD133, Ki-67 and AXL in 509 stage I-IV CRC cases of the Singapore dataset. Supplementary table 3. Statistical associations between pairs of factors in the surgery only (A) and surgery/chemotherapy (B) stage II/III groups in the Singapore dataset. Supplementary table 4. A. Univariate and multivariate analysis (Cox proportional hazards regression) of resection-chemotherapy stage II/III patient group. B. Final multivariate model (Cox proportional hazards regression) of resection-chemotherapy stage II/III patient group. Supplementary table 5. Statistical association between expression levels of TGF-α and EphA2 using Spearman's Rank Correlation in GSE17536, GSE39582, GSE14333 and The Cancer Genome Atlas (TCGA). Within each dataset the value of Rho and associated p-value is reported.

IR-induced changes in cell surface expression of death receptors

Role of EFNA1 in invasion and migration of colorectal cancer cells.

EphA2 and overall survival in stage II and III CRC.

Clinical relevance of EphA2 expression in CRC tissues.

Caspase-8 dependent apoptosis induced by IR

In a study published in Cell, Dong et al. employ a genome-scale CRISPR screening approach to identify both known and previously uncharacterized regulators of CD8+ T cell activity, highlighting the utility of this approach for immunotherapeutic target discovery.

In a study published in Cell, Riquelme et al. unravel intratumoural microbial events associated with long-term survival in pancreatic ductal adenocarcinoma and illustrate that tumour microbiome composition, which is influenced by gut–tumour microbial crosstalk, influences the host immune response and natural history.

NaTuRe RevIeWS | CliniCal OnCOlOgyIn 2016, KeYNoTe-024 established the superior efficacy of first-line pembrolizumab over chemotherapy for metastatic non-small-cell lung cancer (NSClC) with a programmed cell death 1 ligand 1 (PD-l1) tumour proportion score (TPS) ≥50%.Now, overall survival (oS) data from the second interim analysis of KeYNoTe-042, which investigated the efficacy of pembrolizumab in patients with a lower PD-l1 TPS, have been reported.The phase III trial enrolled 1,274 patients with previously untreated, PD-l1-positive (TPS ≥1%), locally advanced or metastatic NSClC without a sensitizing EGFR or ALK alteration.Patients were randomized 1:1 to receive pembrolizumab or platinum-based chemotherapy.The primary end point was oS across three predefined subgroups (TPS ≥50%, ≥20% and ≥1%).At a median follow-up duration of 12.8 months, oS was significantly longer in patients receiving pembrolizumab than in those receiving chemotherapy across all PD-l1 subgroups (TPS ≥50% HR 0.69, 95% CI 0.56-0.85,P = 0.0003; TPS ≥20% HR 0.77, 95% CI 0.64-0.92,P = 0.0020; TPS ≥1% HR 0.81, 95% CI 0.71-0.93,P = 0.0018).median oS for pembrolizumab versus chemotherapy was 20.0 versus 12.2 months, 17.7 versus 13.0 months and 16.7 versus 12.1 months for the TPS ≥50%, ≥20% and ≥1% subgroups, respectively.Any grade (63% versus 90%) and grade ≥3 (18% versus 42%) treatment-related adverse events (TRAEs) were lower with pembrolizumab.In each arm, TRAEs led to death in 2% and to treatment discontinuation in 9% of patients.Overall, these findings have led the FDA to extend the indication for pembrolizumab to patients with a PD-l1 TPS as low as 1%.