Cancer Research on Prevention and Treatment    2022, Vol. 49 Issue (06) : 546-551     DOI: 10.3971/j.issn.1000-8578.2022.21.1296
|
Immune Checkpoint PD-1-based Mechanisms of Tumor Immune Resistance and Strategies for Re-treatment After Drug Resistance
LI Yuxin1,2,3, JIN Feng1,2,3
1. Department of Oncology, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China; 2. Department of Oncology, Affiliated Cancer Hospital of Guizhou Medical University, Guiyang 550008, China; 3. Department of Oncology, Clinical Medical College of Guizhou Medical University, Guiyang 550025, China
Download: PDF(3627 KB)   ( 80 )   HTML ()
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks
Abstract Immunotherapy is considered as the fourth cancer treatment after surgery, radiotherapy and chemotherapy. With the in-depth research on immunotherapy in recent years, especially immuno-checkpoint inhibitors, PD-1/PD-L1 pathway inhibitors have been approved for the treatment of many cancer species. But due to the immune response of tumor cells through multiple drug-resistant mechanisms, immuno-checkpoint blockade has some problems, such as low overall response rate, primary or secondary drug resistance and so on. This paper expounds the mechanism of tumor immune resistance and explores strategies for further treatment after drug resistance, which provides a new theoretical and clinical basis for improving the response rate of immune checkpoint inhibitors and reducing the probability of immune resistance.
Keywords Immunotherapy      Immune checkpoint blockade      Immune resistance      Re-treatment after immune resistance     
ZTFLH:  R730.51  
Fund:National Natural Science Foundation of China (No. 82060556); Science and Technology Project of Guizhou Province (No. [2018]2755); The Science and Technology Fund Project of Guizhou Provincial Health Commission (No. gzwkj2021-049, No. gzwki2021-050)
Issue Date: 16 June 2022
 Cite this article:   
LI Yuxin,JIN Feng. Immune Checkpoint PD-1-based Mechanisms of Tumor Immune Resistance and Strategies for Re-treatment After Drug Resistance[J]. Cancer Research on Prevention and Treatment, 2022, 49(06): 546-551.
 URL:  
http://www.zlfzyj.com/EN/10.3971/j.issn.1000-8578.2022.21.1296
http://www.zlfzyj.com/EN/Y2022/V49/I06/546
Service
E-mail this article
E-mail Alert
RSS
Articles by authors
LI Yuxin
JIN Feng
[1] Huang C, Li M, Liu B, et al. Relating Gut Microbiome and Its
Modulating Factors to Immunotherapy in Solid Tumors: A
Systematic Review[J]. Front Oncol, 2021, 11 : 64211 0.
[2] Kong X, Lu P, Liu C, et al. A combination of PD?1 /PD?L1 inhibitors: The prospect of overcoming the weakness of tumor
immunotherapy (Review)[J]. Mol Med Rep, 2021, 23(5): 362.
[3] Zhang X, Schwartz JC, Guo X, et al. Structural and functional
analysis of the costimulatory receptor programmed death-1[J].
Immunity, 2004, 20(3): 337-347.
[4] Han Y, Liu D, Li L. PD-1/PD-L1 pathway: current researches in
cancer[J]. Am J Cancer Res, 2020, 10(3): 727-742.
[5] Wang Z, Wu X. Study and analysis of antitumor resistance
mechanism of PD1/PD-L1 immune checkpoint blocker[J]. Cancer
Med, 2020, 9(21): 8086-8121.
[6] Rizvi NA, Hellmann MD, 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.
[7] Patel SA, Minn AJ. Combination Cancer Therapy with Immune
Checkpoint Blockade: Mechanisms and Strategies[J]. Immunity,
2018, 48(3): 417-433.
[8] Zaretsky JM, Garcia-Diaz A, Shin DS, et al. Mutations Associated
with Acquired Resistance to PD-1 Blockade in Melanoma[J]. N
Engl J Med, 2016, 375(9): 819-829.
[9] Sade-Feldman M, Jiao YJ, Chen JH, et al. Resistance to checkpoint
blockade therapy through inactivation of antigen presentation[J].
Nat Commun, 2017, 8(1): 11 36.
[10] Lei Q, Wang D, Sun K, et al. Resistance Mechanisms of Anti-PD1/
PDL1 Therapy in Solid Tumors[J]. Front Cell Dev Biol, 2020, 8: 672.
[11 ] Sun C, Mezzadra R, Schumacher TN. Regulation and Function of
the PD-L1 Checkpoint[J]. Immunity, 2018, 48(3): 434-452.
[12] Zhao S, Ren S, Jiang T, et al. Low-Dose Apatinib Optimizes
Tumor Microenvironment and Potentiates Antitumor Effect of
PD-1/PD-L1 Blockade in Lung Cancer[J]. Cancer Immunol Res,
2019, 7(4): 630-643.
[13] Kim K, Park S, Park SY, et al. Single-cell transcriptome analysis
reveals TOX as a promoting factor for T cell exhaustion and a
predictor for anti-PD-1 responses in human cancer[J]. Genome
Med, 2020, 12(1): 22.
[14] Zhou J, Tang Z, Gao S, et al. Tumor-Associated Macrophages:
Recent Insights and Therapies[J]. Front Oncol, 2020, 10: 188.
[15] Shi T, Ma Y, Yu L, et al. Cancer Immunotherapy: A Focus on the
Regulation of Immune Checkpoints[J]. Int J Mol Sci, 2018, 1 9(5):

1389.

[16] Casadei B, Argnani L, Morigi A, et al. Effectiveness of
chemotherapy after anti-PD-1 blockade failure for relapsed and
refractory Hodgkin lymphoma[J]. Cancer Med, 2020, 9(21):
7830-7836.
[17] Suzuki S, Toyoma S, Kawasaki Y, et al. Clinical Outcomes of
Cetuximab and Paclitaxel after Progression on Immune Checkpoint
Inhibitors in Recurrent or Metastatic Head and Neck Squamous
Cell Carcinoma[J]. Medicina (Kaunas), 2021, 57(11 ): 11 51.
[18] Falvo P, Orecchioni S, Hillje R, et al. Cyclophosphamide and
Vinorelbine Activate Stem-Like CD8+ T Cells and Improve Anti-
PD-1 Efficacy in Triple-Negative Breast Cancer[J]. Cancer Res,
2021, 81(3): 685-697.
[19] Wang C, Liu Y, Dong L, et al. Efficacy of Decitabine plus Anti-
PD-1 Camrelizumab in Patients with Hodgkin Lymphoma Who
Progressed or Relapsed after PD-1 Blockade Monotherapy[J].
Clin Cancer Res, 2021, 27(10): 2782-2791.
[20] Ramjiawan RR, Griffioen AW, Duda DG. Anti-angiogenesis
for cancer revisited: Is there a role for combinations with
immunotherapy?[J]. Angiogenesis, 2017, 20(2): 185-204.
[21] Lee CH, Shah AY, Rasco D, et al. Lenvatinib plus pembrolizumab
in patients with either treatment-naive or previously treated
metastatic renal cell carcinoma (Study 111 /KEYNOTE-146): a
phase 1b/2 study[J]. Lancet Oncol, 2021, 22(7): 946-958.
[22] Yang Y, Huang H, Li T, et al. Axitinib Reverses Resistance to Anti-
Programmed Cell Death-1 Therapy in a Patient With Renal Cell
Carcinoma[J]. Front Immunol, 2021, 12: 728750.
[23] Zhao S, Ren S, Jiang T, et al. Low-Dose Apatinib Optimizes
Tumor Microenvironment and Potentiates Antitumor Effect of
PD-1/PD-L1 Blockade in Lung Cancer[J]. Cancer Immunol Res,
2019, 7(4): 630-643.
[24] Yan Z, Ma J, Yao S, et al. Anti-Angiogenic Agent Combined with
Anti-PD-1 Immunotherapy Showed Activity in Patients With
Classical Hodgkin Lymphoma Who Have Failed Immunotherapy:
A Retrospective Case Report Study[J]. Front Immunol, 2021, 1 2:
727464.
[25] Chang JY, Mehran RJ, Feng L, et al. Stereotactic ablative
radiotherapy for operable stageⅠnon-small-cell lung cancer
(revised STARS): long-term results of a single-arm, prospective
trial with prespecified comparison to surgery[J]. Lancet Oncol,
2021, 22(10): 1448-1457.
[26] Benson KRK, Sandhu N, Zhang C, et al. Local Recurrence
Outcomes of Colorectal Cancer Oligometastases Treated With
Stereotactic Ablative Radiotherapy[J]. Am J Clin Oncol, 2021,
44(11 ): 559-564.
[27] Yeo ELL, Li YQ, Soo KC, et al. Combinatorial strategies of
radiotherapy and immunotherapy in nasopharyngeal carcinoma[J].
Chin Clin Oncol, 2018, 7(2): 15.
[28] Formenti SC, Rudqvist NP, Golden E, et al. Radiotherapy induces
responses of lung cancer to CTLA-4 blockade[J]. Nat Med, 2018,
24(12): 1845-1851.
[29] Leighl NB, Redman MW, Rizvi N, et al. Phase Ⅱ study of
durvalumab plus tremelimumab as therapy for patients with
previously treated anti-PD-1/PD-L1 resistant stage Ⅳ squamous
cell lung cancer (Lung-MAP substudy S1400F, NCT03373760)[J].
J Immunother Cancer, 2021, 9(8): e002973.
[30] Kawashima S, Inozume T, Kawazu M, et al. TIGIT/CD155 axis
mediates resistance to immunotherapy in patients with melanoma
with the inflamed tumor microenvironment[J]. J Immunother
Cancer, 2021, 9(11 ): e003134.
[31] Chauvin JM, Zarour HM. TIGIT in cancer immunotherapy[J]. J
Immunother Cancer, 2020, 8(2): e000957.
[32] Wang J, Sun J, Liu LN, et al. Siglec-15 as an immune suppressor
and potential target for normalization cancer immunotherapy[J].
Nat Med, 2019, 25(4): 656-666.
[33] Velikova T, Krastev B, Lozenov S, et al. Antibiotic-Related
Changes in Microbiome: The Hidden Villain behind Colorectal
Carcinoma Immunotherapy Failure[J]. Int J Mol Sci, 2021, 22(4):
1754.
[34] Davar D, Dzutsev AK, McCulloch JA, et al. Fecal microbiota
transplant overcomes resistance to anti-PD-1 therapy in melanoma
patients[J]. Science, 2021, 371(6529): 595-602.
[35] Qi Z, Xu Z, Zhang L, et al. Overcoming resistance to immune
checkpoint therapy in PTEN-null prostate cancer by intermittent
anti-PI3Kα/β/δ treatment[J]. Nat Commun, 2022, 13(1): 182.
[36] Iwata TN, Sugihara K, Wada T, et al. [Fam-] trastuzumab
deruxtecan (DS-8201a)-induced antitumor immunity is facilitated
by the anti-CTLA-4 antibody in a mouse model[J]. PLoS One,
2019, 14(10): e0222280.
[37] Tian X, Zhu Q, Zhang Z. Durable Clinical Response to Immune
and Targeted Therapies in an Elderly Man with Synchronous
Gastric (HER2+) and Bladder Cancers: Case Report and
Literature Review[J]. Onco Targets Ther, 2021, 14: 3701-3708.
[38] Catenacci DVT, Kang YK, Park H, et al. Margetuximab plus
pembrolizumab in patients with previously treated, HER2-positive
gastro-oesophageal adenocarcinoma (CP-MGAH22-05): a singlearm,
phase 1b-2 trial[J]. Lancet Oncol, 2020, 21(8): 1066-1076.
[39] Shekarian T, Sivado E, Jallas AC, et al. Repurposing rotavirus
vaccines for intratumoral immunotherapy can overcome resistance
to immune checkpoint blockade[J]. Sci Transl Med, 2019,
11 (515): eaat5025.
[40] Fang DD, Tang Q, Kong Y, et al. MDM2 inhibitor APG-11 5
exerts potent antitumor activity and synergizes with standard-ofcare
agents in preclinical acute myeloid leukemia models[J]. Cell
Death Discov, 2021, 7(1): 90.
[41] Cheng Y, Lemke-Miltner CD, Wongpattaraworakul W, et al. In
situ immunization of a TLR9 agonist virus-like particle enhances
anti-PD1 therapy[J]. J Immunother Cancer, 2020, 8(2): e000940.

Related articles from Frontiers Journals
[1] YANG Junyuan, CAI Hongbing. Countermeasures and Mechanisms of Drug Resistance in Immunotherapy for Cervical Cancer[J]. Cancer Research on Prevention and Treatment, 2022, 49(09): 886-892.
[2] YIN Zhucheng, LIANG Xinjun. Research Progress on Combined Immunotherapy for Microsatellite Stable Colorectal Cancer#br#[J]. Cancer Research on Prevention and Treatment, 2022, 49(09): 977-981.
[3] CAO Guangwen. Theoretical Update of Cancer Evo-Dev and Its Role in Targeted Immunotherapy for Hepatocellular Carcinoma[J]. Cancer Research on Prevention and Treatment, 2022, 49(08): 747-755.
[4] KANG Yikun, YUAN Peng. Advances in Treatment of Triple Negative Breast Cancer[J]. Cancer Research on Prevention and Treatment, 2022, 49(08): 812-819.
[5] YIN Zhucheng, LIANG Xinjun. Research Progress on Hyperthermia and Anti-Tumor Immunity[J]. Cancer Research on Prevention and Treatment, 2022, 49(08): 827-831.
[6] XIA Siyu, ZHAO Zitong, LI Li. Correlation Between STK11 Gene Mutation and Immunotherapy of Non-small Cell Lung Cancer[J]. Cancer Research on Prevention and Treatment, 2022, 49(08): 850-854.
[7] CHEN Weichang, SHI Tongguo, ZHU Jinghan, SUN Linqing, LI Juntao. Progress on Immunotherapy of Gastrointestinal Cancer[J]. Cancer Research on Prevention and Treatment, 2022, 49(07): 639-643.
[8] JIN Tongtong, ZHOU Chuan, WANG Chao, DA Zijian, ZHOU Fenghai, . Research Hotspots and Frontiers of Immunotherapy for Prostate Cancer: A Visual Analysis[J]. Cancer Research on Prevention and Treatment, 2022, 49(07): 667-674.
[9] WU Wei, JING Doudou, CAO Li, PU Feifei, SHAO Zengwu. Current Status and Prospects of Immunotherapy for Osteosarcoma[J]. Cancer Research on Prevention and Treatment, 2022, 49(07): 721-726.
[10] CHEN Bojin, HU Xingyi, ZHAO Jingwen, ZHENG Aihong. Current Status of Immunotherapy in Neoadjuvant Therapy for Gastric Cancer[J]. Cancer Research on Prevention and Treatment, 2022, 49(07): 727-732.
[11] ZHANG Jianning, LIU Congwei. Progress of Novel Treatment Options for Glioma[J]. Cancer Research on Prevention and Treatment, 2022, 49(06): 505-513.
[12] SUN Junzhao, CHENG Gang, ZHANG Jianning. Advances in Treatment of Brain Metastasis from Lung Cancer[J]. Cancer Research on Prevention and Treatment, 2022, 49(06): 522-527.
[13] ZHANG Yu, HE Kunyu, FENG Shiyu. Current Progress in Treatment of Glioma[J]. Cancer Research on Prevention and Treatment, 2022, 49(06): 528-534.
[14] HOU Jian, WANG Junying. Research Progress of Immune Microenvironment in Multiple Myeloma[J]. Cancer Research on Prevention and Treatment, 2022, 49(05): 375-378.
[15] GUO Yang, WU Suqing, WEN Zhaohui. Application Progress of Metal-organic Frameworks in Tumors Therapy[J]. Cancer Research on Prevention and Treatment, 2022, 49(05): 472-477.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed