The role of EGFR inhibitor (EGFRi) in immune cell infiltration and CD8+ T-cell activation in EGFR mutant lung cancer

Li, F.; Lizee, Gregory; Hwu, Patrick; Du, Xuexiang; Deng, Li; Talukder, Amjad H.; Katailiha, Arjun; Zou, Qi; Roszik, Jason; Hawke, David H.; Jackson, Kyle R.; Bradley, Sherille D.; Wang, Y.; Ataullakhanov, Ravshan; Bagaev, Aleksander; Kotlov, Nikita; Svekolkin, Viktor; Miheecheva, Natalia; Frenkel, Felix; Sonnemann, Heather M.

doi:10.1093/annonc/mdz238.004

Cited by 3 publications

(3 citation statements)

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“…When they detect a tumor cell, the interaction between HLA class I molecule with KIR activates NK cells to destroy abnormal cells. EGFR TKIs were shown to increase the expression of HLA class I molecules at the surface of tumor cells [ 12 ]. They also increase the tumor-induced chemotaxis of immune cells, which results in an increased tumor infiltration by immune cells, including NK cells [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

“…EGFR TKIs were shown to increase the expression of HLA class I molecules at the surface of tumor cells [ 12 ]. They also increase the tumor-induced chemotaxis of immune cells, which results in an increased tumor infiltration by immune cells, including NK cells [ 12 ]. In addition, it was reported that erlotinib treatment of tumors with the p.(Leu858Arg) EGFR -mutation enhances the antigen-presenting capabilities of antigen-presenting cells [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

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Durable response of lung carcinoma patients to EGFR tyrosine kinase inhibitors is determined by germline polymorphisms in some immune-related genes

et al. 2023

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Background Non-small cell lung cancer is a very poor prognosis disease. Molecular analyses have highlighted several genetic alterations which may be targeted by specific therapies. In clinical practice, progression-free survival on EGFR TKI treatment is between 12 and 14 months. However, some patients progress rapidly in less than 6 months, while others remain free of progression for 16 months or even longer during EGFR TKI treatment. Methods We sequenced tumor exomes from 135 lung cancer patients (79 with EGFR-wildtype (WT), 56 with EGFR-mutant tumors) enrolled in the ALCAPONE trial (genomic analysis of lung cancers by next generation sequencing for personalized treatment). Results Some germline polymorphisms were enriched in the EGFR-mutant subset compared to EGFR-WT tumors or to a reference population. However, the most interesting observation was the negative impact of some germline SNPs in immunity-related genes on survival on EGFR TKI treatment. Indeed, the presence of one of three particular SNPs in the HLA-DRB5 gene was associated with a decreased PFS on EGFR TKI. Moreover, some SNPs in the KIR3DL1 and KIR3DL2 genes were linked to a decrease in both progression-free and overall survival of patients with EGFR-mutant tumors. Conclusion Our data suggest that SNPs in genes expressed by immune cells may influence the response to targeted treatments, such as EGFR TKIs. This indicates that the impact of these cells may not be limited to modulating the response to immunotherapies. Further studies are needed to determine the exact mechanisms underlying this influence and to identify the associated predictive and prognostic markers that would allow to refine treatments and so improve lung cancer patient outcomes. Trial registration NCT02281214: NGS Genome Analysis in Personalization of Lung Cancer Treatment (ALCAPONE).

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Durable response of lung carcinoma patients to EGFR tyrosine kinase inhibitors is determined by germline polymorphisms in some immune-related genes

et al. 2023

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“…A systematic review has shown that ICIs are not beneficial for patients with EGFR mutant tumors [ 44 ]. Also, lung cancer cell expressing mutated EGFR is associated with decreased immune cell infiltration and T-cell mediated antitumor immunity [ 45 ]. Therefore, it can be estimated that the cold type patients with high EGFR mutation ratio may exhibit immune suppression and avoidance tendency [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

A Pilot Study of Whether the Cold-Heat Syndrome Type is Associated with Treatment Response and Immune Status in Patients with Non-Small Cell Lung Cancer

Choi

Kwon

Choi

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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The cold-heat syndrome type (ZHENG) is one of the essential elements of syndrome differentiation in East Asian Medicine. This pilot study aimed to explore the characteristics of non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs) based on the cold-heat syndrome type. Twenty NSCLC patients treated with ICI monotherapy were included in the study and completed the cold-heat syndrome differentiation questionnaire. Demographic and clinical characteristics of the included patients were obtained through electronic medical records. Additionally, blood samples of 10 patients were analyzed with cytokine level and immune profiling. Patients were divided into two groups of cold type (n = 9) and non-cold type (n = 11), according to the cold symptoms questionnaire’s cutoff point. No significant difference between the two groups was observed in clinical response to ICIs ( p = 0.668 ). Progression-free survival (PFS) seemed to be longer in patients with non-cold type than cold type ( p = 0.332 ). In patients with adenocarcinoma, the non-cold type showed longer PFS than the cold type ( p = 0.036 ). Also, there were more patients with PD-L1 negative in the cold type compared to the non-cold type ( p = 0.050 ). In immune profiling, the proportion of effector memory CD8 T-cells was higher in patients with cold type than with non-cold type ( p = 0.015 ), and the proportion of terminal effector CD8 T-cells was lower in patients with cold type than with non-cold type ( p = 0.005 ). This pilot study has shown the potential for differences in prognosis and immune status between patients with cold and non-cold types. Hopefully, it provides essential information and insight into NSCLC patients’ characteristics from the perspective of syndrome differentiation. Further large-scale observational studies and intervention studies are required.

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Phosphoprotein dynamics of interacting tumor and T cells by HySic

Ibáñez-Molero,

Pruijs,

Atmopawiro

et al. 2023

Preprint

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Functional interactions between cytotoxic T cells and tumor cells are central to anti-cancer immunity. Some of the proteins involved, particularly immune checkpoints expressed by T cells, serve as promising clinical targets in immunotherapy. However, our understanding of the complexity and dynamics of the interactions between tumor cells and T cells is only rudimentary. Here we present HySic (for Hybrid quantification of SILAC (Stable Isotope Labelling by Amino acids in Cell culture)-labeled interacting cells) as a new method to quantify protein and phosphorylation dynamics between and within physically interacting (heterotypic) cells. We show that co-cultured HLA/antigen-matched tumor and T cells engage in physical and stable interactions, allowing for in-depth HySic analysis. This method does not require physical separation of the two cell types for subsequent MS proteome and phosphoproteome measurement using label free quantification (LFQ). We demonstrate that HySic can be used to unravel proteins contributing to functional T cell:tumor cell interactions. We validated HySic with established interactions, including those mediating IFN-gamma signaling. Using HySic we identified the RHO/RAC/PAK1 signaling pathway to be activated upon interaction of T cells and tumor cells. Pharmacologic inhibition of PAK1 sensitized tumor cells to T cell killing. Thus, HySic is a new and simple method to study short-term protein signaling dynamics in physically interacting cells, which can be easily extended to other biological systems.

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The role of EGFR inhibitor (EGFRi) in immune cell infiltration and CD8+ T-cell activation in EGFR mutant lung cancer

Cited by 3 publications

References 0 publications

Durable response of lung carcinoma patients to EGFR tyrosine kinase inhibitors is determined by germline polymorphisms in some immune-related genes

Durable response of lung carcinoma patients to EGFR tyrosine kinase inhibitors is determined by germline polymorphisms in some immune-related genes

A Pilot Study of Whether the Cold-Heat Syndrome Type is Associated with Treatment Response and Immune Status in Patients with Non-Small Cell Lung Cancer

Phosphoprotein dynamics of interacting tumor and T cells by HySic

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