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In a recent Strategic Organization essay, Arend analyzed four papers as contributions to entrepreneurship theory. He concluded that progress toward building unique-to-field conceptualizations is impeded because contributions in the domain are not sufficiently novel, do not cover the breadth of the phenomenon, and fail to offer normative guidance to practicing entrepreneurs. In this essay, we respond to these conclusions by examining the premise behind the evaluation of theory progress used to derive them, and then drawing on insights from the philosophy of science research to introduce a collective-evolutionary perspective as an alternative for the appraisal of entrepreneurship theory. Our alternative view shifts the focus from single papers toward evaluating theory as a collection of contributions that appear over time. Under this perspective, it is the degree to which newer theories take up insights from prior theory in an evolutionary fashion that serves as a key indicator of progress. Recognizing this, we advocate for a path toward productive theorizing in entrepreneurship where borrowing insights from prior cross-disciplinary theory is a strength rather than weakness, where wide-scope theory is important at the research program level while narrow scope is appropriate for individual contributions, and where obsession over the novelty of theory concepts undermines the continuity needed to produce a reliable body of knowledge.

Strong immune responses in primary colorectal cancer correspond with better patient survival following surgery compared with tumors with predominantly stromal microenvironments. However, biomarkers to identify patients with colorectal cancer liver metastases (CRLM) with good prognosis following surgery for oligometastatic disease remain elusive. The aim of this study was to determine the practical application of a simple histological assessment of immune cell infiltration and stromal content in predicting outcome following synchronous resection of primary colorectal cancer and CRLM and to interrogate the underlying functional biology that drives disease progression. Samples from patients undergoing synchronous resection of primary colorectal cancer and CRLM were evaluated in detail through histological assessment, panel genomic and bulk transcriptomic assessment, IHC, and GeoMx spatial transcriptomics (ST) analysis. High immune infiltration of metastases was associated with improved cancer-specific survival. Bulk transcriptomic analysis was confounded by stromal content, but ST demonstrated that the invasive edge of the metastases of long-term survivors was characterized by adaptive immune cell populations enriched for type II IFN signaling and MHC-class II antigen presentation. In contrast, patients with poor prognosis demonstrated increased abundance of regulatory T cells and neutrophils with enrichment of Notch and TGFβ signaling pathways at the metastatic tumor center. In summary, histological assessment can stratify outcomes in patients undergoing synchronous resection of CRLM, suggesting that it has potential as a prognostic biomarker. Furthermore, ST analysis has revealed significant intratumoral and interlesional heterogeneity and identified the underlying transcriptomic programs driving each phenotype.Significance:Spatial transcriptomics uncovers heterogeneity between patients, between matched lesions in the same patient, and within individual lesions and identifies drivers of metastatic progression in colorectal cancer with reactive and suppressed immune microenvironments.

All supplementary figures and supplementary tables 1 and 2 from the manuscript