A cellular and spatial atlas of TP53-associated tissue remodeling defines a multicellular tumor ecosystem in lung adenocarcinoma

Travis, W. D. et al. The 2015 World Health Organization classification of lung tumors: impact of genetic, clinical and radiologic advances since the 2004 classification. J. Thorac. Oncol. 10, 1243–1260 (2015).

Article  PubMed  Google Scholar 

The Cancer Genome Atlas Research. Network Comprehensive genomic characterization of squamous cell lung cancers. Nature 489, 519–525 (2012).

The Cancer Genome Atlas Research Network. Comprehensive molecular profiling of lung adenocarcinoma. Nature 511, 543–550 (2014).

Hanna, N. H. et al. Therapy for stage IV non-small-cell lung cancer with driver alterations: ASCO and OH (CCO) joint guideline update. J. Clin. Oncol. 39, 1040–1091 (2021).

Article  CAS  PubMed  Google Scholar 

Howlader, N. et al. The effect of advances in lung-cancer treatment on population mortality. N. Engl. J. Med. 383, 640–649 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Herbst, R. S., Morgensztern, D. & Boshoff, C. The biology and management of non-small cell lung cancer. Nature 553, 446–454 (2018).

Article  CAS  PubMed  Google Scholar 

Forde, P. M. et al. Neoadjuvant nivolumab plus chemotherapy in resectable lung cancer. N. Engl. J. Med. 386, 1973–1985 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Non-small cell lung cancer treatment. National Cancer Institute https://www.cancer.gov/types/lung/patient/non-small-cell-lung-treatment-pdq (2021).

Campbell, J. D. et al. Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas. Nat. Genet. 48, 607–616 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Halvorsen, A. R. et al. TP53 mutation spectrum in smokers and never smoking lung cancer patients. Front. Genet. 7, 85 (2016).

Article  PubMed  PubMed Central  Google Scholar 

Kaubryte, J. & Lai, A. G. Pan-cancer prognostic genetic mutations and clinicopathological factors associated with survival outcomes: a systematic review. npj Precis. Oncol. 6, 27 (2022).

Article  CAS  Google Scholar 

Al Bakir, M. et al. The evolution of non-small cell lung cancer metastases in TRACERx. Nature 616, 534–542 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Van Egeren, D. et al. Genomic analysis of early-stage lung cancer reveals a role for TP53 mutations in distant metastasis. Sci. Rep. 12, 19055 (2022).

Article  PubMed  PubMed Central  Google Scholar 

Duffy, M. J., Synnott, N. C., O’Grady, S. & Crown, J. Targeting p53 for the treatment of cancer. Semin. Cancer Biol. 79, 58–67 (2022).

Article  CAS  PubMed  Google Scholar 

Bykov, V. J. N., Eriksson, S. E., Bianchi, J. & Wiman, K. G. Targeting mutant p53 for efficient cancer therapy. Nat. Rev. Cancer 18, 89–102 (2018).

Article  CAS  PubMed  Google Scholar 

Zhu, G. et al. Mutant p53 in cancer progression and targeted therapies. Front. Oncol. 10, 595187 (2020).

Article  PubMed  PubMed Central  Google Scholar 

Uehara, I. & Tanaka, N. Role of p53 in the regulation of the inflammatory tumor microenvironment and tumor suppression. Cancers 10, 219 (2018).

Article  PubMed  PubMed Central  Google Scholar 

Shi, D. & Jiang, P. A different facet of p53 function: regulation of immunity and inflammation during tumor development. Front. Cell Dev. Biol. 9, 762651 (2021).

Article  PubMed  PubMed Central  Google Scholar 

Hodis, E. et al. Stepwise-edited, human melanoma models reveal mutations’ effect on tumor and microenvironment. Science 376, eabi8175 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Efe, G., Rustgi, A. K. & Prives, C. p53 at the crossroads of tumor immunity. Nat. Cancer 5, 983–995 (2024).

Article  PubMed  Google Scholar 

Skoulidis, F. et al. STK11/LKB1 mutations and PD-1 inhibitor resistance in KRAS-mutant lung adenocarcinoma. Cancer Discov. 8, 822–835 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Biton, J. et al. TP53, STK11, and EGFR mutations predict tumor immune profile and the response to anti-PD-1 in lung adenocarcinoma. Clin. Cancer Res. 24, 5710–5723 (2018).

Article  CAS  PubMed  Google Scholar 

Dong, Z. Y. et al. Potential predictive value of TP53 and KRAS mutation status for response to PD-1 blockade immunotherapy in lung adenocarcinoma. Clin. Cancer Res. 23, 3012–3024 (2017).

Article  CAS  PubMed  Google Scholar 

Leader, A. M. et al. Single-cell analysis of human non-small cell lung cancer lesions refines tumor classification and patient stratification. Cancer Cell 39, 1594–1609 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Davis, A. P. et al. Efficacy of immunotherapy in KRAS-mutant non-small-cell lung cancer with comutations. Immunotherapy 13, 941–952 (2021).

Article  CAS  PubMed  Google Scholar 

Scalera, S. et al. KEAP1 and TP53 frame genomic, evolutionary, and immunologic subtypes of lung adenocarcinoma with different sensitivity to immunotherapy. J. Thorac. Oncol. 16, 2065–2077 (2021).

Article  CAS  PubMed  Google Scholar 

Stuart, T. et al. Comprehensive integration of single-cell data. Cell 177, 1888–1902 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dudley, A. C. Tumor endothelial cells. Cold Spring Harb. Perspect. Med. 2, a006536 (2012).

Article  PubMed  PubMed Central  Google Scholar 

Cooke, V. G. et al. Pericyte depletion results in hypoxia-associated epithelial-to-mesenchymal transition and metastasis mediated by Met signaling pathway. Cancer Cell 21, 66–81 (2012).

Article  CAS  PubMed  PubMed Central  Google Scholar 

De Zuani, M. et al. Single-cell and spatial transcriptomics analysis of non-small cell lung cancer. Nat. Commun. 15, 4388 (2024).

Article  PubMed  PubMed Central  Google Scholar 

Takano, Y. et al. Spatially resolved gene expression profiling of tumor microenvironment reveals key steps of lung adenocarcinoma development. Nat. Commun. 15, 10637 (2024).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Greenwald, A. C. et al. Integrative spatial analysis reveals a multi-layered organization of glioblastoma. Cell 187, 2485–2501 (2024).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Li, R. et al. Mapping single-cell transcriptomes in the intra-tumoral and associated territories of kidney cancer. Cancer Cell 40, 1583–1599 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

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