Review Article
 

Neoantigens in Cancer Immunotherapy: An Overview with a Focus on Non-small Cell Lung Cancer and Pancreatic Ductal Adenocarcinoma

Abstract

Non-small cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC) figure prominently in the list of prevalent and resistant cancers that reveal significant differences in response to immunotherapy. Neoantigens, specific antigens resulting from tumor mutations, play an important role in provoking immune responses and the success of immunotherapy. This review scrutinizes the quantitative and qualitative differences in neoantigens in NSCLC and PDAC and their impact on the efficacy of immunotherapy. The evidence suggests that the higher mutational burden, greater diversity, and different quality of neoantigens in NSCLC compared with PDAC are among the key drivers contributing to the enhanced susceptibility to immunotherapy in this cancer. These differences could pave the way for the development of personalized therapies and novel strategies to improve treatment outcomes in resistant cancers.

1. Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 May-Jun;74(3):229-263. doi: 10.3322/caac.21834. Epub 2024 Apr 4. PMID: 38572751.
2. Eskandari-Malayeri F, Rezaei M. Immune checkpoint inhibitors as mediators for immunosuppression by cancer-associated fibroblasts: a comprehensive review. Front Immunol. 2022;13:996145.
3. Siegel RL, Kratzer TB, Giaquinto AN, Sung H, Jemal A. Cancer statistics, 2025. CA Cancer J Clin. 2025;75(1):10-45.
4. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-49.
5. Kumar M, Sarkar A. Current therapeutic strategies and challenges in NSCLC treatment: a comprehensive review. Exp Oncol. 2022;44(1):7-16.
6. Orth M, Metzger P, Gerum S, Mayerle J, Schneider G, Belka C, et al. Pancreatic ductal adenocarcinoma: biological hallmarks, current status, and future perspectives of combined modality treatment approaches. Radiat Oncol. 2019;14(1):141.
7. Shekarchian S, Eghtedardoost M, Golshahi H, Behrouzfar H, Fakhroueian Z, Yaraee R. A Novel Nanodrug Suppresses Lung Cancer Growth and Metastasis in C57BL/6 Mouse Model by Altering CD8+ Cell Infiltration and Oxidative Stress. Iran J Allergy Asthma Immunol. 2025:1-21.
8. Gupta SL, Basu S, Soni V, Jaiswal RK. Immunotherapy: an alternative promising therapeutic approach against cancers. Mol Biol Rep. 2022;49(10):9903-9913.
9. Subramaniam DS, Liu SV, Giaccone G. Novel approaches in cancer immunotherapy. Discov Med. 2016;21(116):267-74.
10. Szeto GL, Finley SD. Integrative Approaches to Cancer Immunotherapy. Trends Cancer. 2019;5(7):400-410.
11. Hendriks LEL, Remon J, Faivre-Finn C, Garassino MC, Heymach JV, Kerr KM, et al. Non-small-cell lung cancer. Nat Rev Dis Primers. 2024;10(1):71.
12. Non-Small Cell Lung Cancer Treatment (PDQ®)–Patient Version. May 23, 2025. Accessed [Date of access]. https://www.cancer.gov/types/lung/patient/non-small-cell-lung-treatment-pdq#:~:text=Key%20Points, to%20 get%20a%20second%20opinion.
13. Heineman DJ, Daniels JM, Schreurs WH. Clinical staging of NSCLC: current evidence and implications for adjuvant chemotherapy. Ther Adv Med Oncol. 2017;9(9):599-609.
14. Alduais Y, Zhang H, Fan F, Chen J, Chen B. Non-small cell lung cancer (NSCLC): A review of risk factors, diagnosis, and treatment. Medicine (Baltimore). 2023;102(8):e32899.
15. Kaur P, Singh SK, Mishra MK, Singh S, Singh R. Promising Combinatorial Therapeutic Strategies against Non-Small Cell Lung Cancer. Cancers (Basel). 2024;16(12).
16. Sham NO, Zhao L, Zhu Z, Roy TM, Xiao H, Bai Q, et al. Immunotherapy for Non-small Cell Lung Cancer: Current Agents and Potential Molecular Targets. Anticancer Res. 2022;42(7):3275-84.
17. Yoh K, Matsumoto S, Furuya N, Nishino K, Miyamoto S, Oizumi S, et al. Comprehensive assessment of PD-L1 expression, tumor mutational burden and oncogenic driver alterations in non-small cell lung cancer patients treated with immune checkpoint inhibitors. Lung Cancer. 2021;159:128-34.
18. Olivares-Hernández A, González Del Portillo E, Tamayo-Velasco Á, Figuero-Pérez L, Zhilina-Zhilina S, Fonseca-Sánchez E, et al. Immune checkpoint inhibitors in non-small cell lung cancer: from current perspectives to future treatments-a systematic review. Ann Transl Med. 2023;11(10):354.
19. Kang J, Zhang C, Zhong WZ. Neoadjuvant immunotherapy for non-small cell lung cancer: State of the art. Cancer Commun (Lond). 2021;41(4):287-302.
20. Shukla N, Hanna N. Neoadjuvant and Adjuvant Immunotherapy in Early-Stage Non-Small Cell Lung Cancer. Lung Cancer (Auckl). 2021;12:51-60.
21. Hansen T, Hill J, Tincknell G, Siu D, Brungs D, Clingan P, et al. Evidence for the evolving role of neoadjuvant and perioperative immunotherapy in resectable non-small cell lung cancer. Explor Target Antitumor Ther. 2024;5(6):1247-60.
22. Ying H, Kimmelman AC, Bardeesy N, Kalluri R, Maitra A, DePinho RA. Genetics and biology of pancreatic ductal adenocarcinoma. Genes Dev. 2025;39(1-2):36-63.
23. Singh G, Kutcher D, Lally R, Rai V. Targeting Neoantigens in Pancreatic Ductal Adenocarcinoma. Cancers (Basel). 2024;16(11).
24. Joseph AM, Al Aiyan A, Al-Ramadi B, Singh SK, Kishore U. Innate and adaptive immune-directed tumour microenvironment in pancreatic ductal adenocarcinoma. Front Immunol. 2024;15:1323198.
25. Olaoba OT, Yang M, Adelusi TI, Maidens T, Kimchi ET, Staveley-O'Carroll KF, Li G. Targeted Therapy for Highly Desmoplastic and Immunosuppressive Tumor Microenvironment of Pancreatic Ductal Adenocarcinoma. Cancers (Basel). 2024;16(8).
26. Alzhrani R, Alsaab HO, Vanamal K, Bhise K, Tatiparti K, Barari A, et al. Overcoming the Tumor Microenvironmental Barriers of Pancreatic Ductal Adenocarcinomas for Achieving Better Treatment Outcomes. Adv Ther (Weinh). 2021;4(6).
27. Pang Y, Holmes MV, Chen Z, Kartsonaki C. A review of lifestyle, metabolic risk factors, and blood-based biomarkers for early diagnosis of pancreatic ductal adenocarcinoma. J Gastroenterol Hepatol. 2019;34(2):330-45.
28. Gardiner A, Kidd J, Elias MC, Young K, Mabey B, Taherian N, et al. Pancreatic Ductal Carcinoma Risk Associated With Hereditary Cancer-Risk Genes. J Natl Cancer Inst. 2022;114(7):996-1002.
29. McGarry JL, Creavin B, Kelly ME, Gallagher TK. Risk of pancreatic ductal adenocarcinoma associated with carriage of BRCA1 and/or BRCA2 mutation: A systematic review and meta-analysis. J Surg Oncol. 2022;126(6):1028-37.
30. Keane MG, Horsfall L, Rait G, Pereira SP. A case-control study comparing the incidence of early symptoms in pancreatic and biliary tract cancer. BMJ Open. 2014;4(11):e005720.
31. Gullo L, Tomassetti P, Migliori M, Casadei R, Marrano D. Do early symptoms of pancreatic cancer exist that can allow an earlier diagnosis? Pancreas. 2001;22(2):210-3.
32. Kunovsky L, Tesarikova P, Kala Z, Kroupa R, Kysela P, Dolina J, Trna J. The Use of Biomarkers in Early Diagnostics of Pancreatic Cancer. Can J Gastroenterol Hepatol. 2018;2018:5389820.
33. Mangge H, Niedrist T, Renner W, Lyer S, Alexiou C, Haybaeck J. New Diagnostic and Therapeutic Aspects of Pancreatic Ductal Adenocarcinoma. Curr Med Chem. 2017;24(28):3012-24.
34. Sarantis P, Koustas E, Papadimitropoulou A, Papavassiliou AG, Karamouzis MV. Pancreatic ductal adenocarcinoma: Treatment hurdles, tumor microenvironment and immunotherapy. World J Gastrointest Oncol. 2020;12(2):173-81.
35. Poyia F, Neophytou CM, Christodoulou MI, Papageorgis P. The Role of Tumor Microenvironment in Pancreatic Cancer Immunotherapy: Current Status and Future Perspectives. Int J Mol Sci. 2024;25(17).
36. Macherla S, Laks S, Naqash AR, Bulumulle A, Zervos E, Muzaffar M. Emerging Role of Immune Checkpoint Blockade in Pancreatic Cancer. Int J Mol Sci. 2018;19(11).
37. Kabacaoglu D, Ciecielski KJ, Ruess DA, Algül H. Immune Checkpoint Inhibition for Pancreatic Ductal Adenocarcinoma: Current Limitations and Future Options. Front Immunol. 2018;9:1878.
38. Levink IJM, Brosens LAA, Rensen SS, Aberle MR, Olde Damink SSW, Cahen DL, et al. Neoantigen Quantity and Quality in Relation to Pancreatic Cancer Survival. Front Med (Lausanne). 2021;8:751110.
39. Liang H, Xu Y, Chen M, Zhao J, Zhong W, Liu X, et al. Characterization of Somatic Mutations That Affect Neoantigens in Non-Small Cell Lung Cancer. Front Immunol. 2021;12:749461.
40. McGranahan N, Furness AJ, Rosenthal R, Ramskov S, Lyngaa R, Saini SK, et al. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science. 2016;351(6280):1463-9.
41. Su S, Chen F, Xu M, Liu B, Wang L. Recent advances in neoantigen vaccines for treating non-small cell lung cancer. Thorac Cancer. 2023;14(34):3361-8.
42. De Mattos-Arruda L, Vazquez M, Finotello F, Lepore R, Porta E, Hundal J, et al. Neoantigen prediction and computational perspectives towards clinical benefit: recommendations from the ESMO Precision Medicine Working Group. Ann Oncol. 2020;31(8):978-90.
43. Sasada T. [Cancer immunotherapy targeting neoantigens derived from tumor-specific gene mutations]. Nihon Rinsho. 2017;75(2):189-95.
44. Mardis ER. Neoantigens and genome instability: impact on immunogenomic phenotypes and immunotherapy response. Genome Med. 2019;11(1):71.
45. Levine AJ, Jenkins NA, Copeland NG. The Roles of Initiating Truncal Mutations in Human Cancers: The Order of Mutations and Tumor Cell Type Matters. Cancer Cell. 2019;35(1):10-15.
46. Habel K. Resistance of Polyoma Virus Immune Animals to Transplanted Polyoma Tumors. Proc Soc Exp Biol Med. 1961;106:722-5.
47. Sim MJW, Sun PD. T Cell Recognition of Tumor Neoantigens and Insights Into T Cell Immunotherapy. Front Immunol. 2022;13:833017.
48. Bobisse S, Foukas PG, Coukos G, Harari A. Neoantigen-based cancer immunotherapy. Ann Transl Med. 2016;4(14):262.
49. Schumacher TN, Schreiber RD. Neoantigens in cancer immunotherapy. Science. 2015;348(6230):69-74.
50. Ohue Y. [Current Topics of Cancer Antigen]. Gan To Kagaku Ryoho. 2019;46(10):1467-72.
51. Xie N, Shen G, Gao W, Huang Z, Huang C, Fu L. Neoantigens: promising targets for cancer therapy. Signal Transduct Target Ther. 2023;8(1):9.
52. Jiang T, Shi T, Zhang H, Hu J, Song Y, Wei J, et al. Tumor neoantigens: from basic research to clinical applications. J Hematol Oncol. 2019;12(1):93.
53. Wu DW, Jia SP, Xing SJ, Ma HL, Wang X, Tang QY, et al. Personalized neoantigen cancer vaccines: current progression, challenges and a bright future. Clin Exp Med. 2024;24(1):229.
54. Ward JP, Gubin MM, Schreiber RD. The Role of Neoantigens in Naturally Occurring and Therapeutically Induced Immune Responses to Cancer. Adv Immunol. 2016;130:25-74.
55. Wang P, Chen Y, Wang C. Beyond Tumor Mutation Burden: Tumor Neoantigen Burden as a Biomarker for Immunotherapy and Other Types of Therapy. Front Oncol. 2021;11:672677.
56. Zou XL, Li XB, Ke H, Zhang GY, Tang Q, Yuan J, et al. Prognostic Value of Neoantigen Load in Immune Checkpoint Inhibitor Therapy for Cancer. Front Immunol. 2021;12:689076.
57. Lang F, Schrörs B, Löwer M, Türeci Ö, Sahin U. Identification of neoantigens for individualized therapeutic cancer vaccines. Nat Rev Drug Discov. 2022;21(4):261-82.
58. Pao SC, Chu MT, Hung SI. Therapeutic Vaccines Targeting Neoantigens to Induce T-Cell Immunity against Cancers. Pharmaceutics. 2022;14(4).
59. Liontos M, Anastasiou I, Bamias A, Dimopoulos MA. DNA damage, tumor mutational load and their impact on immune responses against cancer. Ann Transl Med. 2016;4(14):264.
60. Goodman AM, Kato S, Bazhenova L, Patel SP, Frampton GM, Miller V, et al. Tumor Mutational Burden as an Independent Predictor of Response to Immunotherapy in Diverse Cancers. Mol Cancer Ther. 2017;16(11):2598-608.
61. Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015;348(6230):124-8.
62. Xiong A, Wang J, Zhou C. Immunotherapy in the First-Line Treatment of NSCLC: Current Status and Future Directions in China. Front Oncol. 2021;11:757993.
63. Bear AS, Vonderheide RH, O'Hara MH. Challenges and Opportunities for Pancreatic Cancer Immunotherapy. Cancer Cell. 2020;38(6):788-802.
64. Li KY, Yuan JL, Trafton D, Wang JX, Niu N, Yuan CH, et al. Pancreatic ductal adenocarcinoma immune microenvironment and immunotherapy prospects. Chronic Dis Transl Med. 2020;6(1):6-17.
65. Looi CK, Chung FF, Leong CO, Wong SF, Rosli R, Mai CW. Therapeutic challenges and current immunomodulatory strategies in targeting the immunosuppressive pancreatic tumor microenvironment. J Exp Clin Cancer Res. 2019;38(1):162.
66. Li F, Wu H, Du X, Sun Y, Rausseo BN, Talukder A, et al. Epidermal Growth Factor Receptor-Targeted Neoantigen Peptide Vaccination for the Treatment of Non-Small Cell Lung Cancer and Glioblastoma. Vaccines (Basel). 2023;11(9):1460.
67. Li F, Deng L, Jackson KR, Talukder AH, Katailiha AS, Bradley SD, et al. Neoantigen vaccination induces clinical and immunologic responses in non-small cell lung cancer patients harboring EGFR mutations. J Immunother Cancer. 2021;9(7):e002531.
68. Shi C, Wang Y, Xue J, Zhou X. Immunotherapy for EGFR-mutant advanced non-small-cell lung cancer: Current status, possible mechanisms and application prospects. Front Immunol. 2022;13:940288.
69. Al Bakir M, Reading JL, Gamble S, Rosenthal R, Uddin I, Rowan A, et al. Clonal driver neoantigen loss under EGFR TKI and immune selection pressures. Nature. 2025;639(8056):1052-59.
70. Dimou A, Grewe P, Sidney J, Sette A, Norman PJ, Doebele RC. HLA Class I Binding of Mutant EGFR Peptides in NSCLC Is Associated With Improved Survival. J Thorac Oncol. 2021 Jan;16(1):104-112. doi: 10.1016/j.jtho.2020.08.023. Epub 2020 Sep 11. PMID: 32927123; PMCID: PMC7797166.
71. Issue Information. Immunol Rev. 2023;310(1):1-3.
72. Balachandran VP, Łuksza M, Zhao JN, Makarov V, Moral JA, Remark R, et al. Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer. Nature. 2017;551(7681):512-6.
73. Hu Z, Ott PA, Wu CJ. Towards personalized, tumour-specific, therapeutic vaccines for cancer. Nat Rev Immunol. 2018;18(3):168-82.
74. Blass E, Ott PA. Advances in the development of personalized neoantigen-based therapeutic cancer vaccines. Nat Rev Clin Oncol. 2021;18(4):215-29.
75. Kumari K, Singh A, Chaudhary A, Singh RK, Shanker A, Kumar V, Haque R. Neoantigen Identification and Dendritic Cell-Based Vaccines for Lung Cancer Immunotherapy. Vaccines (Basel). 2024;12(5).
76. Singh G, Kutcher D, Lally R, Rai V. Targeting Neoantigens in Pancreatic Ductal Adenocarcinoma. Cancers (Basel). 2024;16(11):2101.
77. Pant S, Wainberg ZA, Weekes CD, Furqan M, Kasi PM, Devoe CE, et al. Lymph-node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: the phase 1 AMPLIFY-201 trial. Nat Med. 2024;30(2):531-42.
78. Stefanoudakis D, Frountzas M, Schizas D, Michalopoulos NV, Drakaki A, Toutouzas KG. Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer. Curr Issues Mol Biol. 2024;46(4):2827-44.
79. Lennerz V, Doppler C, Fatho M, Dröge A, Schaper S, Gennermann K, et al. T-cell receptors identified by a personalized antigen-agnostic screening approach target shared neoantigen KRAS Q61H. Front Immunol. 2025;16:1509855.
80. Steinbuck MP, Cabana-Puig X, Palmer E, Jung MM, Williams T, Osaer K, et al. AMP-peptide vaccination against multiple p53 mutant epitopes promotes lymph node delivery to generate potent, functional T cell immunity. Cancer Res. 2024;84(6_Supplement):4099.
81. Duffy MJ, Synnott NC, Crown J. Mutant p53 as a target for cancer treatment. Eur J Cancer. 2017;83:258-265.
82. Rojas LA, Sethna Z, Soares KC, Olcese C, Pang N, Patterson E, et al. Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer. Nature. 2023;618(7963):144-50.
83. Ding Z, Li Q, Zhang R, Xie L, Shu Y, Gao S, et al. Personalized neoantigen pulsed dendritic cell vaccine for advanced lung cancer. Signal Transduct Target Ther. 2021;6(1):26.
84. Ott PA, Hu Z, Keskin DB, Shukla SA, Sun J, Bozym DJ, et al. An immunogenic personal neoantigen vaccine for patients with melanoma. Nature. 2017;547(7662):217-21.
85. Magoola M, Niazi SK. Current Progress and Future Perspectives of RNA-Based Cancer Vaccines: A 2025 Update. Cancers (Basel). 2025;17(11):1882.
86. Singh P, Khatib MN, R R, Kaur M, Srivastava M, Barwal A, et al. Advancements and challenges in personalized neoantigen-based cancer vaccines. Oncol Rev. 2024;19:1541326.
87. Li F, Deng L, Jackson KR, Talukder AH, Katailiha AS, Bradley SD, et al. Neoantigen vaccination induces clinical and immunologic responses in non-small cell lung cancer patients harboring EGFR mutations. J Immunother Cancer. 2021;9(7).
88. Yang H, Wang Y, Jia Z, Wang Y, Yang X, Wu P, et al. Characteristics of T-Cell Receptor Repertoire and Correlation With EGFR Mutations in All Stages of Lung Cancer. Front Oncol. 2021;11:537735.
89. Skoulidis F, Goldberg ME, Greenawalt DM, Hellmann MD, Awad MM, Gainor JF, et al. STK11/LKB1 Mutations and PD-1 Inhibitor Resistance in KRAS-Mutant Lung Adenocarcinoma. Cancer Discov. 2018;8(7):822-35.
90. Minne RL, Luo NY, Traynor AM, Huang M, DeTullio L, Godden J, et al. Genomic and Immune Landscape Comparison of MET Exon 14 Skipping and MET-Amplified Non-small Cell Lung Cancer. Clin Lung Cancer. 2024;25(6):567-576.e1.
91. Su S, Luo P, Zhang J, Zhang B, Zou J, Huang Z. P14. 12 MET amplification and immune checkpoint inhibitor efficacy in NSCLC. J Thorac Oncol. 2021;16(3):S334.
92. Lu C, Dong XR, Zhao J, Zhang XC, Chen HJ, Zhou Q, et al. Association of genetic and immuno-characteristics with clinical outcomes in patients with RET-rearranged non-small cell lung cancer: a retrospective multicenter study. J Hematol Oncol. 2020;13(1):37.
93. Jiang B, Hu L, Dong D, Guo Z, Wei W, Wang C, et al. TP53 or CDKN2A/B covariation in ALK/RET/ROS1-rearranged NSCLC is associated with a high TMB, tumor immunosuppressive microenvironment and poor prognosis. J Cancer Res Clin Oncol. 2023;149(12):10041-52.
94. Ingels J, De Cock L, Stevens D, Mayer RL, Thery F, Sanchez GS, et al. Neoantigen-targeted dendritic cell vaccination in lung cancer patients induces long-lived T cells exhibiting the full differentiation spectrum. Cell Rep Med. 2024;5(5).
95. Robertson J, Salm M, Dangl M. Adoptive cell therapy with tumour-infiltrating lymphocytes: the emerging importance of clonal neoantigen targets for next-generation products in non-small cell lung cancer. Immuno-Oncology Technology. 2019;3:1-7.
96. Case K, Kennedy K, Kujtan L, Subramanian J. The role of tumour neoantigens in the differential response to immunotherapy (IO) in EGFR and BRAF mutated lung cancers: Quantity or quality? Ann Oncol. 2019;30:v513.
97. Lin J, Liu J, Hao SG, Lan B, Zheng XB, Xiong JN, et al. An EGFR L858R mutation identified in 1862 Chinese NSCLC patients can be a promising neoantigen vaccine therapeutic strategy. Front Immunol. 2022;13:1022598.
98. Hachey SJ, Forsythe AG, Keshava HB, Hughes CCW. ImmuniT Platform for Improved Neoantigen Prediction in Lung Cancer. bioRxiv. 2025.
99. Fu X, Liu S, Cao D, Li C, Ji H, Wang G. Med23 deficiency reprograms the tumor microenvironment to promote lung tumorigenesis. Br J Cancer. 2024;130(5):716-27.
100. Yan Y, Gao Z, Han H, Zhao Y, Zhang Y, Ma X, Chen H. NRAS expression is associated with prognosis and tumor immune microenvironment in lung adenocarcinoma. J Cancer Res Clin Oncol. 2022;148(3):565-75.
101. Chen GL, Kong DX, Lin Y. Neo-Antigen-Reactive T Cells Immunotherapy for Colorectal Cancer: A More Personalized Cancer Therapy Approach. Global Challenges. 2023;7(11):2200186.
102. Hattori T, Maso L, Araki KY, Koide A, Hayman J, Akkapeddi P, et al. Creating MHC-restricted neoantigens with covalent inhibitors that can be targeted by immune therapy. Cancer Discov. 2023;13(1):132-45.
103. Dehem A, Mazieres J, Chour A, Guisier F, Ferreira M, Boussageon M, et al. Characterization of 164 patients with NRAS mutated non-small cell lung cancer (NSCLC). Lung Cancer. 2023;186:107393.
104. Yang P, Qiao Y, Meng M, Zhou Q. Cancer/Testis Antigens as Biomarker and Target for the Diagnosis, Prognosis, and Therapy of Lung Cancer. Front Oncol. 2022;12:864159.
105. Saito K, Nakayama E, Valmori D. Immune Responses to the Cancer Testis Antigen XAGE-1b in Non Small Cell Lung Cancer Caucasian Patients. PLoS One. 2016;11(3):e0150623.
106. Scanlan MJ, Gure AO, Jungbluth AA, Old LJ, Chen YT. Cancer/testis antigens: an expanding family of targets for cancer immunotherapy. Immunol Rev. 2002;188:22-32.
107. Connor AA, Denroche RE, Jang GH, Timms L, Kalimuthu SN, Selander I, et al. Association of Distinct Mutational Signatures With Correlates of Increased Immune Activity in Pancreatic Ductal Adenocarcinoma. JAMA Oncol. 2017;3(6):774-83.
108. Chen YW, Hsiao PJ, Weng CC, Kuo KK, Kuo TL, Wu DC, et al. SMAD4 Loss triggers the phenotypic changes of pancreatic ductal adenocarcinoma cells. BMC Cancer. 2014;14:1.
109. Domchek SM, McWilliams R, Hendifar A, Shroff RT, Leichman L, Epelbaum R, et al. Abstract B102: A phase 2, open-label study of the PARP inhibitor rucaparib in patients with pancreatic cancer and a known deleterious BRCA mutation. Cancer Res. 2015;75(13_Supplement):B102-B.
110. Seeber A, Zimmer K, Kocher F, Puccini A, Xiu J, Nabhan C, et al. Molecular characteristics of BRCA1/2 and PALB2 mutations in pancreatic ductal adenocarcinoma. ESMO Open. 2020;5(6):e000942.
111. Lei M, Gai J, McPhaul TJ, Luo H, Lin P, Liu D, et al. Homologous recombination-DNA damage response defects increase TMB and neoantigen load, but not effector T cell density and clonal diversity in pancreatic cancer. Exp Hematol Oncol. 2025;14(1):86.
112. DeSelm CJ, Tano ZE, Varghese AM, Adusumilli PS. CAR T-cell therapy for pancreatic cancer. J Surg Oncol. 2017;116(1):63-74.
113. Giurini EF, Ralph O, Pappas SG, Gupta KH. Looking Beyond Checkpoint Inhibitor Monotherapy: Uncovering New Frontiers for Pancreatic Cancer Immunotherapy. Mol Cancer Ther. 2025;24(1):18-32.
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Cancer immunotherapy Non-small cell lung cancer Neoantigens Pancreatic ductal adenocarcinoma

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Eskandari-Malayeri F, Shekarchian S, Mortaz E. Neoantigens in Cancer Immunotherapy: An Overview with a Focus on Non-small Cell Lung Cancer and Pancreatic Ductal Adenocarcinoma. Iran J Allergy Asthma Immunol. 2026;:1-13.