China Oncology ›› 2024, Vol. 34 ›› Issue (4): 368-379.doi: 10.19401/j.cnki.1007-3639.2024.04.004
• Article • Previous Articles Next Articles
LIN Yicong(), WANG Yue, XUE Qianqian, ZHENG Qiang, JIN Yan, HUANG Ziling, LI Yuan(
)
Received:
2023-12-13
Revised:
2024-02-25
Online:
2024-04-30
Published:
2024-05-17
Contact:
LI Yuan
Share article
CLC Number:
LIN Yicong, WANG Yue, XUE Qianqian, ZHENG Qiang, JIN Yan, HUANG Ziling, LI Yuan. Clinical pathological characteristics and immune microenvironment significance of EGFR T790M mutation in non-small cell lung cancer patients and its prognostic implications[J]. China Oncology, 2024, 34(4): 368-379.
Tab. 1
Clinicopathological characteristics of de novo and acquired T790M in advanced NSCLC"
Characteristics | Total (n=82) | de novo T790M n(%) | Acquired T790M n (%) | P value |
---|---|---|---|---|
Total n | 82 | 15 (18.29) | 67 (81.71) | |
Gender | 0.383 4 | |||
Male | 32 | 4 (26.67) | 28 (41.79) | |
Female | 50 | 11 (73.33) | 39 (58.21) | |
Age/year | 0.255 4 | |||
<63 | 42 | 10 (66.67) | 32 (47.76) | |
≥63 | 40 | 5 (33.33) | 35 (52.24) | |
Histological differentiation | 0.026 4* | |||
High/medium | 6 | 3 (20.00) | 3 (4.48) | |
Low | 33 | 8 (53.33) | 25 (37.31) | |
NA | 43 | 4 (26.67) | 39 (58.21) | |
Specimen type | 0.036 5* | |||
Tissue biopsy | 46 | 9 (60.00) | 37 (55.23) | |
Surgery | 16 | 6 (40.00) | 13 (19.40) | |
Liquid biopsy | 17 | 0 (0.00) | 17 (25.37) | |
PD-L1 expression | 0.011 0* | |||
Negative (<1%) | 33 | 5 (33.33) | 28 (41.79) | |
Positive (≥1%) | 24 | 9 (60.00) | 15 (22.39) | |
NA | 25 | 1 (6.67) | 24 (35.82) |
Fig. 1
Characterization of concurrent molecular alterations of de novo and acquired T790M in NSCLC A: Characterization of concurrent molecular alterations of de novo and acquired T790M in NSCLC; B: Characterization of concurrent molecular alterations of de novo and acquired T790M in advanced NSCLC; C: Forest plot of univarite Cox regression analysis in advanced NSCLC-acquired T790M; D: Median duration of remission of EGFR-TKI for acquired T790M mutation in advanced NSCLC."
Fig. 2
The comparison between de novo and acquired T790M mutations in NSCLC concerning the utilization of third-generation EGFR TKI and subsequent prognostic analysis A: Efficacy of de novo T790M mutations in advanced NSCLC using third-generation EGFR TKI; B: Efficacy of acquired T790M mutations in advanced NSCLC using third-generation EGFR TKI; C-D: Median TD and median PFS of de novo T790M in advanced NSCLC; E-F: Median TD and median PFS of acquired T790M in advanced NSCLC; G: Survival curves for de novo and acquired T790M in advanced NSCLC; H-I: Proportion of de novo and acquired T790M recurrences; J-K: Proportion of de novo and acquired T790M metastases."
Tab. 2
Characterization of molecular alterations in advanced NSCLC acquired T790M based on efficacy groupings"
Characteristics | Total (n = 61) | PD (n = 39) n(%) | Non-PD (n = 22) n(%) | P value |
---|---|---|---|---|
Total | 61 | 39 (100.00) | 22 (100.00) | |
EGFR 19Del | 1.000 0 | |||
Negative | 31 | 20 (51.28) | 11 (50.00) | |
Positive | 30 | 19 (48.72) | 11 (50.00) | |
EGFR L858R | 0.684 2 | |||
Negative | 34 | 23 (58.97) | 11 (50.00) | |
Positive | 27 | 16 (41.03) | 11 (50.00) | |
TP53 | 0.528 2 | |||
Negative | 37 | 22 (56.41) | 15 (68.18) | |
Positive | 24 | 17 (43.59) | 7 (31.82) |
Fig. 3
Characterization of immune cell subpopulations in acquired T790M A: Comparison of immune cell density in tumor and stromal regions in acquired T790M; B-G: Schematic representation of multiple immunofluorescence histochemical expression; H-Q: Comparison of immune cell density between EGFR with tumor suppressor mutations and EGFR mutations alone."
Fig. 4
Characterization of spatial distribution of immune cells in acquired T790M after treatment with EGFR TKI A-J: Comparison of the average distance between tumor cells and immune cells in 2 groups, EGFR with tumor suppressor gene mutations and EGFR mutations alone; K-T: Comparative assessment of immune cell infiltration density within a 200 μm radius at the peripheries of cancer nests between the EGFR with tumor suppressor gene mutation and EGFR mutation alone cohorts."
[1] | SIEGEL R L, MILLER K D, FUCHS H E, et al. Cancer statistics, 2021[J]. CA A Cancer J Clin, 2021, 71(1): 7-33. |
[2] |
DUMA N, SANTANA-DAVILA R, MOLINA J R. Non-small cell lung cancer: epidemiology, screening, diagnosis, and treatment[J]. Mayo Clin Proc, 2019, 94(8): 1623-1640.
doi: S0025-6196(19)30070-9 pmid: 31378236 |
[3] | MILLER M, HANNA N. Advances in systemic therapy for non-small cell lung cancer[J]. BMJ, 2021, 375: n2363. |
[4] | DA CUNHA SANTOS G, SHEPHERD F A, TSAO M S. EGFR mutations and lung cancer[J]. Annu Rev Pathol, 2011, 6: 49-69. |
[5] |
HARRISON P T, VYSE S, HUANG P H. Rare epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer[J]. Semin Cancer Biol, 2020, 61: 167-179.
doi: S1044-579X(19)30302-5 pmid: 31562956 |
[6] |
LIM S M, SYN N L, CHO B C, et al. Acquired resistance to EGFR targeted therapy in non-small cell lung cancer: mechanisms and therapeutic strategies[J]. Cancer Treat Rev, 2018, 65: 1-10.
doi: S0305-7372(18)30016-1 pmid: 29477930 |
[7] | LI W H, QIU T, GUO L, et al. Primary and acquired EGFR T790M-mutant NSCLC patients identified by routine mutation testing show different characteristics but may both respond to osimertinib treatment[J]. Cancer Lett, 2018, 423: 9-15. |
[8] |
RIZVI N A, HELLMANN M D, SNYDER A, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer[J]. Science, 2015, 348(6230): 124-128.
doi: 10.1126/science.aaa1348 pmid: 25765070 |
[9] | ISOMOTO K, HARATANI K, HAYASHI H, et al. Impact of EGFR-TKI treatment on the tumor immune microenvironment in EGFR mutation-positive non-small cell lung cancer[J]. Clin Cancer Res, 2020, 26(8): 2037-2046. |
[10] | GUEGUEN P, METOIKIDOU C, DUPIC T, et al. Contribution of resident and circulating precursors to tumor-infiltrating CD8+ T cell populations in lung cancer[J]. Sci Immunol, 2021, 6(55): eabd5778. |
[11] |
PATIL N S, NABET B Y, MÜLLER S, et al. Intratumoral plasma cells predict outcomes to PD-L1 blockade in non-small cell lung cancer[J]. Cancer Cell, 2022, 40(3): 289-300.e4.
doi: 10.1016/j.ccell.2022.02.002 pmid: 35216676 |
[12] | JIN Y, XUE Q Q, SHEN X X, et al. PD-L1 expression and comprehensive molecular profiling predict survival in non-small cell lung cancer: a real-world study of a large Chinese cohort[J]. Clin Lung Cancer, 2022, 23(1): 43-51. |
[13] | ZHENG Q, HUANG Y, ZENG X, et al. Clinicopathological and molecular characteristics associated with PD-L1 expression in non-small cell lung cancer: a large-scale, multi-center, real-worldstudy in China[J]. J Cancer Res Clin Oncol, 2021, 147(5): 1547-1556. |
[14] | WANG X, HUI S, TAN C, et al. Comprehensive analysis of immune subtypes reveals the prognostic value of cytotoxicity and FAP+ fibroblasts in stomach adenocarcinoma[J]. Cancer Immunol Immunother, 2023, 72(6): 1763-1778. |
[15] | CHEN Z, FILLMORE C M, HAMMERMAN P S, et al. Non-small cell lung cancers: a heterogeneous set of diseases[J]. Nat Rev Cancer, 2014, 14(8): 535-546. |
[16] |
GELATTI A C Z, DRILON A, SANTINI F C. Optimizing the sequencing of tyrosine kinase inhibitors (TKIs) in epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC)[J]. Lung Cancer, 2019, 137: 113-122.
doi: S0169-5002(19)30661-0 pmid: 31568888 |
[17] | NEEL D S, BIVONA T G. Resistance is futile: overcoming resistance to targeted therapies in lung adenocarcinoma[J]. NPJ Precis Oncol, 2017, 1: 3. |
[18] | DENIS M G, VALLÉE A, THÉOLEYRE S. EGFR T790M resistance mutation in non small-cell lung carcinoma[J]. Clin Chim Acta, 2015, 444: 81-85. |
[19] | WANG S Y, YAN B, ZHANG Y W, et al. Different characteristics and survival in non-small cell lung cancer patients with primary and acquired EGFR T790M mutation[J]. Int J Cancer, 2019, 144(11): 2880-2886. |
[20] | AKBAY E A, KOYAMA S, CARRETERO J, et al. Activation of the PD-1 pathway contributes to immune escape in EGFR-driven lung tumors[J]. Cancer Discov, 2013, 3(12): 1355-1363. |
[21] | VOKES N I, CHAMBERS E, NGUYEN T, et al. Concurrent TP53 mutations facilitate resistance evolution in EGFR-mutant lung adenocarcinoma[J]. J Thorac Oncol, 2022, 17(6): 779-792. |
[22] | GOU L Y, LI A N, YANG J J, et al. The coexistence of MET over-expression and an EGFR T790M mutation is related to acquired resistance to EGFR tyrosine kinase inhibitors in advanced non-small cell lung cancer[J]. Oncotarget, 2016, 7(32): 51311-51319. |
[23] | ZALAQUETT Z, CATHERINE RITA HACHEM M, KASSIS Y, et al. Acquired resistance mechanisms to osimertinib: the constant battle[J]. Cancer Treat Rev, 2023, 116: 102557. |
[24] | BRUNO T C. New predictors for immunotherapy responses sharpen our view of the tumor microenvironment[J]. Nature, 2020, 577(7791): 474-476. |
[25] | HOU H L, QIN K, LIANG Y, et al. Concurrent TP53 mutations predict poor outcomes of EGFR-TKI treatments in Chinese patients with advanced NSCLC[J]. Cancer Manag Res, 2019, 11: 5665-5675. |
[26] | OFFIN M, CHAN J M, TENET M, et al. Concurrent RB1 and TP53 alterations define a subset of EGFR-mutant lung cancers at risk for histologic transformation and inferior clinical outcomes[J]. J Thorac Oncol, 2019, 14(10): 1784-1793. |
[27] | BITON J, MANSUET-LUPO A, PÉCUCHET N, et al. TP53, STK11, and EGFR mutations predict tumor immune profile and the response to anti-PD-1 in lung adenocarcinoma[J]. Clin Cancer Res, 2018, 24(22): 5710-5723. |
Viewed | ||||||
Full text |
|
|||||
Abstract |
|
|||||
沪ICP备12009617
Powered by Beijing Magtech Co. Ltd