Prostate cancer cells synergistically defend against CD8+ T cells by secreting exosomal PD-L1
© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd..
BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) remains fatal and incurable, despite a variety of treatments that can delay disease progression and prolong life. Immune checkpoint therapy is a promising treatment. However, emerging evidence suggests that exosomal programmed necrosis ligand 1 (PD-L1) directly binds to PD-1 on the surface of T cells in the drain lineage lymph nodes or neutralizes administered PD-L1 antibodies, resulting in poor response to anti-PD-L1 therapy in mCRPC.
MATERIALS AND METHODS: Western blotting and immunofluorescence were performed to compare PD-L1 levels in exosomes derived from different prostate cancer cells. PC3 cells were subcutaneously injected into nude mice, and then ELISA assay was used to detect human specific PD-L1 in exosomes purified from mouse serum. The function of CD8+ T cells was detected by T cell mediated tumor cell killing assay and FACS analysis. A subcutaneous xenograft model was established using mouse prostate cancer cell RM1, exosomes with or without PD-L1 were injected every 3 days, and then tumor size and weight were analyzed to evaluate the effect of exosomal PD-L1.
RESULTS: Herein, we found that exosomal-PD-L1 was taken up by tumor cells expressing low levels of PD-L1, thereby protecting them from T-cell killing. Higher levels of PD-L1 were detected in exosomes derived from the highly malignant prostate cancer PC3 and DU145 cell lines. Moreover, exosomal PD-L1 was taken up by the PD-L1-low-expressing LNCaP cell line and inhibited the killing function of CD8-T cells on tumor cells. The growth rate of RM1-derived subcutaneous tumors was decreased after knockdown of PD-L1 in tumor cells, whereas the growth rate recovered following exosomal PD-L1 tail vein injection. Furthermore, in the serum of mice with PCa subcutaneous tumors, PD-L1 was mainly present on exosomes.
CONCLUSION: In summary, tumor cells share PD-L1 synergistically against T cells through exosomes. Inhibition of exosome secretion or prevention of PD-L1 sorting into exosomes may improve the therapeutic response of prostate tumors to anti-PD-L1 therapy.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
|---|---|
| Enthalten in: |
Cancer medicine - 12(2023), 15 vom: 27. Aug., Seite 16405-16415 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Li, Dameng [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Anti-PD-L1 therapy |
|---|
| Anmerkungen: |
Date Completed 01.09.2023 Date Revised 02.09.2023 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1002/cam4.6275 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM36001321X |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM36001321X | ||
| 003 | DE-627 | ||
| 005 | 20231226082110.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1002/cam4.6275 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1199.xml |
| 035 | |a (DE-627)NLM36001321X | ||
| 035 | |a (NLM)37501397 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Li, Dameng |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Prostate cancer cells synergistically defend against CD8+ T cells by secreting exosomal PD-L1 |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 01.09.2023 | ||
| 500 | |a Date Revised 02.09.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. | ||
| 520 | |a BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) remains fatal and incurable, despite a variety of treatments that can delay disease progression and prolong life. Immune checkpoint therapy is a promising treatment. However, emerging evidence suggests that exosomal programmed necrosis ligand 1 (PD-L1) directly binds to PD-1 on the surface of T cells in the drain lineage lymph nodes or neutralizes administered PD-L1 antibodies, resulting in poor response to anti-PD-L1 therapy in mCRPC | ||
| 520 | |a MATERIALS AND METHODS: Western blotting and immunofluorescence were performed to compare PD-L1 levels in exosomes derived from different prostate cancer cells. PC3 cells were subcutaneously injected into nude mice, and then ELISA assay was used to detect human specific PD-L1 in exosomes purified from mouse serum. The function of CD8+ T cells was detected by T cell mediated tumor cell killing assay and FACS analysis. A subcutaneous xenograft model was established using mouse prostate cancer cell RM1, exosomes with or without PD-L1 were injected every 3 days, and then tumor size and weight were analyzed to evaluate the effect of exosomal PD-L1 | ||
| 520 | |a RESULTS: Herein, we found that exosomal-PD-L1 was taken up by tumor cells expressing low levels of PD-L1, thereby protecting them from T-cell killing. Higher levels of PD-L1 were detected in exosomes derived from the highly malignant prostate cancer PC3 and DU145 cell lines. Moreover, exosomal PD-L1 was taken up by the PD-L1-low-expressing LNCaP cell line and inhibited the killing function of CD8-T cells on tumor cells. The growth rate of RM1-derived subcutaneous tumors was decreased after knockdown of PD-L1 in tumor cells, whereas the growth rate recovered following exosomal PD-L1 tail vein injection. Furthermore, in the serum of mice with PCa subcutaneous tumors, PD-L1 was mainly present on exosomes | ||
| 520 | |a CONCLUSION: In summary, tumor cells share PD-L1 synergistically against T cells through exosomes. Inhibition of exosome secretion or prevention of PD-L1 sorting into exosomes may improve the therapeutic response of prostate tumors to anti-PD-L1 therapy | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a CD8+ T cells | |
| 650 | 4 | |a PD-L1 | |
| 650 | 4 | |a anti-PD-L1 therapy | |
| 650 | 4 | |a exosomes | |
| 650 | 4 | |a prostate cancer | |
| 650 | 7 | |a B7-H1 Antigen |2 NLM | |
| 700 | 1 | |a Zhou, Xueying |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Wenxian |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yuxin |e verfasserin |4 aut | |
| 700 | 1 | |a Mu, Chenglong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Xinchun |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Tao |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Gang |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Liang |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Bo |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cancer medicine |d 2012 |g 12(2023), 15 vom: 27. Aug., Seite 16405-16415 |w (DE-627)NLM224388460 |x 2045-7634 |7 nnns |
| 773 | 1 | 8 | |g volume:12 |g year:2023 |g number:15 |g day:27 |g month:08 |g pages:16405-16415 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1002/cam4.6275 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 12 |j 2023 |e 15 |b 27 |c 08 |h 16405-16415 | ||