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Modulating Tumor Microenvironment: A Review on STK11 Immune Properties and Predictive vs Prognostic Role for Non-small-cell Lung Cancer Immunotherapy

  • Lung Cancer (TA Leal, Section Editor)
  • Published:
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Opinion Statement

The quest for immunotherapy (IT) biomarkers is an element of highest clinical interest in both solid and hematologic tumors. In non-small-cell lung cancer (NSCLC) patients, besides PD-L1 expression evaluation with its intrinsic limitations, tissue and circulating parameters, likely portraying the tumor and its stromal/immune counterparts, have been proposed as potential predictors of IT responsiveness. STK11 mutations have been globally labeled as markers of IT resistance. After a thorough literature review, STK11 mutations condition the prognosis of NSCLC patients receiving ICI-containing regimens, implying a relevant biological and clinical significance. On the other hand, waiting for prospective and solid data, the putative negative predictive value of STK11 inactivation towards IT is sustained by less evidence. The physiologic regulation of multiple cellular pathways performed by STK11 likely explains the multifaceted modifications in tumor cells, stroma, and tumor immune microenvironment (TIME) observed in STK11 mutant lung cancer, particularly explored in the molecular subgroup of KRAS co-mutation. IT approaches available thus far in NSCLC, mainly represented by anti-PD-1/PD-L1 inhibitors, are not promising in the case of STK11 inactivation. Perceptive strategies aimed at modulating the TIME, regardless of STK11 status or specifically addressed to STK11-mutated cases, will hopefully provide valid therapeutic options to be adopted in the clinical practice.

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Correspondence to Francesco Facchinetti.

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Giulia Mazzaschi declares that she has no conflict of interest. Alessandro Leonetti has received compensation from AstraZeneca for service as a consultant. Roberta Minari declares that she has no conflict of interest. Letizia Gnetti declares that she has no conflict of interest. Federico Quaini declares that he has no conflict of interest. Marcello Tiseo has received research funding from AstraZeneca, Boehringer Ingelheim, Pfizer, Novartis, Roche, MSD, Otsuka, and Pierre Fabre; and has received compensation for service as a consultant from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Bristol-Myers Squibb, Novartis, Roche, and MSD. Francesco Facchinetti has received compensation from Bristol-Myers Squibb and Roche for service as a consultant.

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Mazzaschi, G., Leonetti, A., Minari, R. et al. Modulating Tumor Microenvironment: A Review on STK11 Immune Properties and Predictive vs Prognostic Role for Non-small-cell Lung Cancer Immunotherapy. Curr. Treat. Options in Oncol. 22, 96 (2021). https://doi.org/10.1007/s11864-021-00891-8

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