PMC5916968_01
Positron-emission tomography (PET)-scanner imaging at baseline (A) and after three cycles of pembrolizumab (B). (A) Patient's baseline PET scan (December 2016): only four infracentimetric hypermetabolic lung nodules are visible [standardized uptake values (SUV) from 2.2 to 5.5]. No evidence of distant metastases elsewhere. (B) Patient's PET scan after three cycles of pembrolizumab (May 2017): diffuse and multiple hypermetabolic lung, liver, subcutaneous tissue, and peritoneal lesions (SUV from 3.5 to 17).
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F1
There was no evidence of other extrapulmonary metastatic spreads (Figure 1A). A PET scan revealed the emergence of multiple new centimetric hypermetabolic lung spots along with increased size and glycolic activity in the previously identified nodules that were associated with multiple new hypermetabolic liver, subcutaneous tissues, and peritoneal lesions (Figure 1B), and showed a rapidly progressive disease over 2 months.
Flow cytometry analysis of myeloid cells comparing the HP with five HD. (A) Higher proportion of monocytes (HLADR+ CD33+, CD14+) and CD16+ monocytes (HLADR+ CD33+, CD14+ CD16+) in HP compared to the HD (pro-inflammatory cells). (B) Increased median fluorescence intensity of PDL1 in monocytes/CD16+ monocytes, and the more important percentage of the immunosuppressive population of Gr-MDSC in the HP patient compared to HD. Abbreviations: HP, hyperprogressive patient; HD, healthy donors; Mono, monocytes; Mono16+, monocytes 16+; GrMDSC, granulocytic myeloid-derived suppressor cells; Mo-MDSC, monocyte-derived suppressor cells; IMC, immature myeloid cells; PBMC, peripheral blood mononuclear cells.
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F2
Figure 2, the HP patient had a higher proportion of monocytes (HLADR+ CD33+, CD14+) and CD16+ monocytes (HLADR+ CD33+, CD14+ CD16+) compared to the HD (Figure 2A). Furthermore, the patient's monocytes and CD16+ monocytes had an increased median fluorescence intensity of PDL1 compared to HD. Additionally, between the live PBMC samples, the percentage of the immunosuppressive population of granulocytic myeloid-derived suppressor cells (Gr-MDSC), defined as CD33+/HLADR-/CD15+/CD14-, was increased in the HP patient (Figure 2B).
Flow cytometry analysis of lymphoid T cells comparing the HP with five HD. HP showed an increased proportion of naive CD4/CD8 and CD4 terminally differentiated cells (TEMRA: effector memory CD45RA+) and a decrease in memory cells (CM/EM). Abbreviations: HP, hyperprogressive patient; HD, healthy donors; CM, central memory; EM, Effector Memory; TEMRA, Terminally differentiated Effector Memory RA+.
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F3
In the lymphoid cell analysis presented in Figure 3, the HP patient presented a shift in CD4 and CD8 differentiation, with an increased proportion of CD4/CD8 naive and CD4 terminally differentiated cells (TEMRA: Effector Memory CD45RA+), and a decrease in memory cells (central memory/effector memory).
Flow cytometry analysis of NK cells comparing the HP with five HD. Increased proportion of NK bright (CD56+ high) cells in HP compared to HD. Conversely, decreased expression of the receptors NKp30 and NKp46 in HP compared to HD. Abbreviations: HP, hyperprogressive patient; HD, healthy donors; NKp30/NKp46, natural cytotoxicity receptors.
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F4
Among natural killer cells (NK cells), the HP patient had an over-expression of NK bright (CD56+ high) cells and an under-expression of the receptors NKp30 and NKp46 (Figure 4).