Correlative Monitoring of Immune Activation and Tissue Damage in Malignant Melanoma—An Algorithm for Identification of Tolerance Breakage During Immune Checkpoint Inhibitor Therapy of Cancer
Abstract
:1. Introduction
2. Theoretical Considerations
3. Results
4. Discussion
5. Materials and Methods
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
Abbreviations
AUC | area under the curve |
CRP | c-reactive protein |
CTLA4 | cytotoxic T-lymphocyte antigen 4 |
IFNγ | interferon gamma |
IL | interleukin |
LDH | lactate dehydrogenase |
NSCLC | non squamous cell lung cancer |
PD-1 | programmed cell death 1 |
S100B | S100 calcium-binding protein B |
TNF | tumor necrosis factor |
ULN | upper limit of normal |
References
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Biomarker | Cancer Entity | Reference |
---|---|---|
Enhanced programmed cell death ligand 1 (PD-L1) expression in the tumor | melanoma, non-small cell lung cancer (NSCLC), renal-cell carcinoma, prostate cancer, colorectal cancer | [5,6,7,8] |
Presence of CD8+tumor-infiltrating lymphocytes | melanoma, NSCLC, renal-cell carcinoma, colorectal cancer | [5,6,7,9,10] |
High tumor mutational burden or neoantigen burden | melanoma, NSCLC, colorectal cancer, urothelial carcinoma | [5,11,12] |
Presence of intratumoral major histocompatibility complex (MHC) class II expression | melanoma | [5,13] |
Presence of intratumoral interferon-γ-immune gene signature | melanoma, head and neck cancer | [5,14] |
Low interleukin (IL)-6 expression in the tumor | colorectal cancer | [15] |
Peripheral blood count: low absolute neutrophils, low absolute monocytes, low myeloid-derived suppressor cells, high FoxP3+ regulatory T cells, high lymphocytes, high eosinophils, high CD19−HLA-DR+ myeloid cells, high CD14+CD16b−HLA-DRhi monocytes | melanoma, NSCLC | [5,16,17,18] |
Low level of c-reactive protein (CRP) in the serum, low relative eosinophil count | uveal melanoma | [19] |
Serum proteome analysis: BDX008 | melanoma | [20] |
Biomarker | Cancer Entity | Reference |
---|---|---|
Peripheral blood count: decreasing FoxP3+ regulatory T cells, increasing absolute lymphocytes, increasing eosinophils, decrease of the neutrophil-to-lymphocyte ratio, decrease of HLA-DR monocytes, increase of total dendritic cells | melanoma, NSCLC | [18,21,22] |
Biomarker | Autoimmune Disease | Reference |
---|---|---|
Serum levels: elevated serum amyloid A, Interleukin (IL)-6, IL-8, eotaxin-1 | Inflammatory Bowel Disease | [25] |
Peripheral blood count: elevated monocytes | Painless autoimmune thyroiditis | [26] |
Peripheral blood count: elevated eosinophils | Grave’s disease | [26] |
Serum levels: IL-6, IL-8, IL-17, IL-21, tumor necrosis factor (TNF)-α | Autoimmune hepatitis | [27,28] |
Peripheral blood count: elevated eosinophils | Autoimmune pneumonitis | [29] |
no. | TNM at TX | TX (Cycles) | TMR IM | TMR Day | irAE (IM) | irAE. Day | best resp. | Survival from TX, Months |
---|---|---|---|---|---|---|---|---|
1 | pT3a, N3c, M1a | ipi. (4) | IL-6 | 62 | - | PR | >89 | |
nivo. (11) | - | thyroiditis (mono.) | 28 | PR | ||||
2 | pT1a, N3, M1c | ipi. (4) | IL-6 | 81 | myositis | 81 | PD | 8.5 |
hepatitis | ||||||||
(IL-6, CRP, mono.) | ||||||||
3 | pT4, N1b, M1c | ipi. (3) | - | - | thyroiditis | 49 | PD | 19 |
4 | pT3a, N3, M1c | ipi. (4) | IL-6 | 16 | hepatitis | 77 | PR | 14 |
(mono., eos.) | ||||||||
nivo. (7) | paradox | - | - | |||||
5 | pT3a, N3, M1c | ipi. (3) | IL-6 | 1 | colitis | 70 | PR | >6 |
(eos.) | ||||||||
pemb. (33) | IL-6 | 8, 141 | myositis (IL-6) | 148 | CR | |||
6 | pTx, N3, M1c | pemb. (7) | paradox | - | - | - | PD | 8 |
7 | pT3b, N3, M1c | pemb. (8) | IL-6 | 5 | pneumonitis | 188 | PR | >11 |
mono. | (IL-6) | |||||||
8 | pT2a, N2b, M1c | nivo. (18) | - | - | - | - | PR | >51 |
nivo.+ | ||||||||
ipi. ((2), 11) | IL-6 | 40 | hepatitis (IL-6, CRP) | 40 | CR | |||
9 | pT4a, N3, M0 | pemb. (9) | - | - | - | - | PD | 8 |
10 | pT4a, N1a | pemb. (19) | IL-6 | 71 | - | - | PD | >13 |
11 | pTx, N0, M1c | pemb. (28) | IL-6 | (21) 141 | - | - | CR | >41 |
12 | pT3b, N1b, M1d | nivo.+ | IL-6 | 6 | neuritis | 6 | CR | 27 |
ipi. (1) | ||||||||
13 | pT4, N1c, M0 | nivo. (3) | - | - | - | - | PD | 14 |
14 | pTx, Nx, M1b | nivo.+ | IL-6 | 28 | thyroiditis, hepatitis | 35 | CR | >25 |
ipi. (1) | (IL-6, CRP) | |||||||
nivo. (7) | - | Pneumonitis (IL-6, CRP, mono.) | 182 | CR | ||||
15 | pT2b, N3c, M1c | nivo.+ | IL-6 | 7 (112) * | thyroiditis, | 21 | CR | >35 |
ipi. (2) | (IL-6, mono.) | |||||||
nivo. (8) | IL-6 | Myositis (IL-6) | 98 | CR | ||||
16 | pTx, N2, M1a | nivo.+ | IL-6 | (4) 39 | rash | 4 | CR | >11 |
ipi. (1) | hypophysitis, pneumonitis | 20 | ||||||
(IL-6, mono.) | 20 | |||||||
17 | pT3a, N1b, M1c | nivo. (1) | IL-6 * | 28 * | vitiligo | 70 | PR | >8 |
nivo. + ipi ((4), 10) | CRP | (eos.) |
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Wahl, R.U.; Leijs, M.; Araujo, A.; Rübben, A. Correlative Monitoring of Immune Activation and Tissue Damage in Malignant Melanoma—An Algorithm for Identification of Tolerance Breakage During Immune Checkpoint Inhibitor Therapy of Cancer. Int. J. Mol. Sci. 2020, 21, 2020. https://doi.org/10.3390/ijms21062020
Wahl RU, Leijs M, Araujo A, Rübben A. Correlative Monitoring of Immune Activation and Tissue Damage in Malignant Melanoma—An Algorithm for Identification of Tolerance Breakage During Immune Checkpoint Inhibitor Therapy of Cancer. International Journal of Molecular Sciences. 2020; 21(6):2020. https://doi.org/10.3390/ijms21062020
Chicago/Turabian StyleWahl, Renate U., Marike Leijs, Arturo Araujo, and Albert Rübben. 2020. "Correlative Monitoring of Immune Activation and Tissue Damage in Malignant Melanoma—An Algorithm for Identification of Tolerance Breakage During Immune Checkpoint Inhibitor Therapy of Cancer" International Journal of Molecular Sciences 21, no. 6: 2020. https://doi.org/10.3390/ijms21062020
APA StyleWahl, R. U., Leijs, M., Araujo, A., & Rübben, A. (2020). Correlative Monitoring of Immune Activation and Tissue Damage in Malignant Melanoma—An Algorithm for Identification of Tolerance Breakage During Immune Checkpoint Inhibitor Therapy of Cancer. International Journal of Molecular Sciences, 21(6), 2020. https://doi.org/10.3390/ijms21062020