Cancer Resistance to Immunotherapy: Comprehensive Insights with Future Perspectives
Abstract
:1. Introduction
2. The Cancer Immune Cycle
3. Innate and Adaptive Immune Responses in the Tumor Microenvironment (TME)
4. Resistance to Cancer Immunotherapy
5. Tumor Factors (Intrinsic) Associated with Immunotherapy Resistance
5.1. Disorders of the Antigenic Determinants of Tumor Cells
5.2. Factors Modulating the Function of the Immune System
5.3. Factors Associated with Resistance to the Effector Immune Response
5.4. Epigenetic Regulation of Cancer Resistance to Immunotherapy
6. Extrinsic Factors Contributing to Tumor Resistance against Immunotherapy
6.1. Tumor-Infiltrating Lymphocytes
6.2. Chemokines
6.3. Vascular-Tumor Microenvironment
6.4. Immuno-Metabolic Products
6.5. Tumor-Associated Macrophages (TAMs)
7. Host Factors Associated with Immunotherapy Resistance
8. Models of Cancer Immunotherapy
8.1. Immune-Checkpoint Inhibitors
8.2. Chemokine Therapies
8.3. Adenosine-Targeting Therapies
8.4. Cell-Based Immunotherapy—Adoptive Cellular Transfer (ACT)
8.5. Vaccines
8.6. Exosomes
8.7. Epigenetic Modulators
8.8. Microbiota
9. Overcoming Cancer Resistance to Immunotherapy
10. Future Directions for Cancer Immunotherapy
11. Combination Therapies
12. Personalized Immunotherapy
13. Adoptive Cell Therapy
14. Overcoming Resistance
15. Novel Immunotherapy Agents
Author Contributions
Funding
Conflicts of Interest
References
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Treatment | Modalities of Combined Immunotherapy | Tumor Type | Phase | Clinical Trial | Ref. |
---|---|---|---|---|---|
Durvalumab + autologous anti-CD19CAR-4-1BB-CD3z EGFRt-expressing CD4+/CD8+ central memory T lymphocytes JCAR014 | Anti- PDL-1 + CAR T cells | Diffuse large B-cell lymphoma | 1 | NCT02706405 | [154] |
Pembrolizumab + CART-EGFRvIII T cells | Anti- PD-1 + CAR T cells | Glioblastoma | 1 | NCT03726515 | [11] |
Inupadenant + EOS-448 | Adenosine A receptor blocker + anti-TIGIT mAB | Advanced solid tumors | 2 | NCT05060432 | [155] |
Ciforadenant ± atezolizumab | Adenosine A receptor blocker + anti-PD-1 | Advanced prostate cancer | 1,1b | NCT02655822 | [156] |
Ciforadenant + daratumumab | Adenosine A receptor blocker + mAb against CD38 | Multiple myeloma | 1 | NCT04280328 | [157] |
AB928/etrumadenant + zimberelimab + enzalutamide | Adenosine A and B receptor blocker + anti-PD-1 + anti-androgen or chemotherapy | Advanced prostate cancer | 2 | NCT04381832 | [158] |
AB928/etrumadenant zimberelimab + AB680 | Adenosine A and B receptor blocker + anti-PD-1 + CD73 inhibitor | Colonic cancer | 2 | NCT04660812 | [158] |
Etrumadenant +PLD + IPI-549 | Adenosine A and B receptor blocker + chemotherapy + PI3K-gamma inhibitor | Breast cancer | 1 | NCT03719326 | [159] |
Bintrafusp alfa | PD-L1 and TGF β inhibitors | Squamous cell carcinoma | 1 | NCT02699515. | [11,152] |
CD19 CAR T-expressing IL7 and CCL19 combined with tislelizumab | IL17, CCL9 chemokine, and PD-1 mAb | Relapsed or refractory B-cell lymphoma | 1 | NCT04381741 | [160] |
HuMax-IL8 + nivolumab | CXCL8-chemokine and PD-1- IC | Head and neck squamous | 2 | NCT04848116 | [123] |
Entinostat plus pembrolizumab | Histone deacetylase inhibitors plus PD-1 blockade | Non-small-cell lung cancer (NSCLC) | 2 | NCT02437136 | [161] |
Autogene cevumeran and atezolizumab | mRNA-based cancer vaccine and anti-PD-L1 | Metastatic tumors | 1 | NCT03289962 | [162] |
Azacitidine and PD-L1 inhibitors | Demethylating agent plus PD-L1 inhibitor | Acute myeloid leukemia | 2 | NCT02775903 | [163] |
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Said, S.S.; Ibrahim, W.N. Cancer Resistance to Immunotherapy: Comprehensive Insights with Future Perspectives. Pharmaceutics 2023, 15, 1143. https://doi.org/10.3390/pharmaceutics15041143
Said SS, Ibrahim WN. Cancer Resistance to Immunotherapy: Comprehensive Insights with Future Perspectives. Pharmaceutics. 2023; 15(4):1143. https://doi.org/10.3390/pharmaceutics15041143
Chicago/Turabian StyleSaid, Sawsan Sudqi, and Wisam Nabeel Ibrahim. 2023. "Cancer Resistance to Immunotherapy: Comprehensive Insights with Future Perspectives" Pharmaceutics 15, no. 4: 1143. https://doi.org/10.3390/pharmaceutics15041143
APA StyleSaid, S. S., & Ibrahim, W. N. (2023). Cancer Resistance to Immunotherapy: Comprehensive Insights with Future Perspectives. Pharmaceutics, 15(4), 1143. https://doi.org/10.3390/pharmaceutics15041143