Tumor-Associated B7-H1 Promotes T-Cell Apoptosis: A Potential Mechanism of Immune Evasion
Nature Medicine, 2002 · paper · Biomedicine
Examines B7-H1, an immune-regulating surface protein, in human tissues. It was found in most cancers examined but not normal tissues, and activated T cells interacting with tumor B7-H1 underwent programmed cell death, suggesting a way tumors evade immune destruction.
3 findings
Substance Fig. 4 legend gives polyclonal T cells as "Purified human T cells (2 × 10^5 cells/well)" cultured with plate-bound control Ig or B7-H1Ig at 10 µg/ml plus anti-CD3 for 72 h, but Methods give "blood T cells (>95% CD3+) at 4 × 10^5 per well" for the same assay.
- p. 6 Fig. 4 legend
Purified human T cells (2 × 105 cells/well)
- p. 7 Methods, apoptosis in polyclonal T cells
at 4 × 105 per well
- p. 6 Fig. 4 legend
(2 × 105 cells/well)
- p. 7
at 4 × 105 per well were precoated cultured in
Only the authors can say what is right here.
Judge's note: Checked the Fig. 4 legend (p6) and the Methods paragraph on polyclonal T-cell apoptosis (p7) in the crops. Both describe the same setup: plate-bound anti-CD3, B7-H1Ig or control Ig at 10 µg/ml, 72 h, and PD-1Ig blockade. One gives 2 × 10^5 cells/well and the other 4 × 10^5. A text search found no other statement that would explain two seeding densities, such as a separate experiment. Only the authors can say which value is correct. The garbled 'precoated cultured' wording raised in reviewer note 6 is judged under C019.
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Reference or label The IFN-γ upregulation of B7-H1 on tumour lines is cited as "(Supplementary Table A online)" twice in the Results (p2) but as "(Supplementary Table 1 online)" in the Discussion (p5).
- p. 2 Results, top left
(Supplementary Table A online)
- p. 5 Discussion
(Supplementary Table 1 online)
Judge's note: Images show 'Supplementary Table A' twice on p2 (left and right columns) and 'Supplementary Table 1' on p5, all supporting the same IFN-γ-induced B7-H1 claim. Every other supplementary item is lettered (Supplementary Figs A, B, C). The supplement is not among the files, so the actual label cannot be checked, but the two pointers are inconsistent and 'A' fits the lettering scheme.
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Reference or label "HBL-100 cells express B7-H1, but not FasL or TRAIL, on their surface (Figs 4a and 3a)". Fig. 4a is a time course of T-cell apoptosis and holds no HBL-100 staining.
- p. 3 Results, HBL-100 paragraph
on their surface (Figs 4a and 3a)
- p. 6 Fig. 4a legend
A time course of apoptosis of activated T cells induced by anti-CD3 and B7-H1Ig
- p. 3 HBL-100 paragraph
(Figs 4a and 3a)
Judge's note: Checked p3 and p6. Fig. 4a plots apoptotic cells (%) against time (h) for polyclonal T cells with anti-CD3/B7-H1Ig. The HBL-100 FACS staining for B7-H1, FasL and TRAIL is in Fig. 3a only (p5). The Fig. 4a pointer is wrong. It may have been meant as Fig. 2a (624mel), but only the authors can say.
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12 minor (typos and the like; most checked by the judge only)
Reference or label "Inclusion of antibody against FasL ... (Fig. 4d) also inhibited the growth of tumor cells by blocking the interaction of Fas and FasL, leading to the inhibition of M15 CTL apoptosis (Fig. 2f)". Fig. 2f has no anti-FasL arm and no apoptosis measure.
- p. 3 Results, right column
leading to the inhibition of M15 CTL apoptosis (Fig. 2f)
- p. 4 Fig. 2f legend
partially neutralized by antibody against B7-H1
Only the authors can say what is right here.
Judge's note: Fig. 2f (p4) shows tumour-cell numbers on days 1, 3 and 5 for Mock/624mel + M15, B7-H1/624mel + mIgG1 + M15 and B7-H1/624mel + 2H1 (anti-B7-H1) + M15. It has no FasL antibody group and no M15 apoptosis data, so it does not show the claimed anti-FasL inhibition of M15 apoptosis. The authors should say which panel was meant.
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Wording Results say anti-B7-H1 "abrogated the resistance of B7-H1/624mel cells to killing by T cells (Fig. 2e and f)", while the Fig. 2f legend says the resistance "can be partially neutralized by antibody against B7-H1".
- p. 2 Results, last line, right column
in the culture medium abrogated the resistance of B7-
- p. 4 Fig. 2f legend
can be partially neutralized by antibody against B7-H1
Only the authors can say what is right here.
Judge's note: In Fig. 2f (p4 image), the B7-H1/624mel + 2H1 + M15 group (▲) stays above the Mock/624mel + M15 group (●) on days 1, 3 and 5 (about 3.4 vs about 0.3 ×10^4/well on day 5). The data and the legend show partial reversal, so 'abrogated' in the text overstates them.
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Typo Subject–verb disagreement: "Our result indicate that B7-H1 binds a non-PD-1 receptor" (p3).
- p. 3 Results, HBL-100 paragraph
Our result indicate that B7-H1 binds
- p. 3 HBL-100 paragraph
Our result indicate that B7-H1 binds a non-PD-1
Judge's note: The p3 crop confirms the wording 'Our result indicate'. It should read 'Our results indicate'.
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Typo The Discussion spells the protein "RACS1" twice ("Recent studies implicate RACS1, a coiled-coil membrane protein"; "whether RACS1 is involved"), but the cited ref. 32 title has "RCAS1".
- p. 5 Discussion
Recent studies implicate RACS1, a coiled-coil
- p. 8 Reference 32
the human tumor-associated antigen, RCAS1
- p. 8 Ref 32
RCAS1
- p. 5 Discussion
whether RACS1 is involved
Judge's note: The p5 crop shows 'RACS1' twice. Ref. 32 on p8 reads '...the human tumor-associated antigen, RCAS1'. This is an internal spelling mismatch with the cited source. (The 614mel point in one reviewer note is handled under C015.)
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Typo The Fig. 3b legend has "After 4 d of culture with HBL100 cells and IL-15", but the cell line is "HBL-100" everywhere else.
- p. 5 Fig. 3 legend b
HBL100 cells and IL-15
Judge's note: The p5 image confirms 'HBL100' without the hyphen in the Fig. 3b legend. The text and the rest of the legend use HBL-100. Cosmetic inconsistency.
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Typo The Fig. 4d legend has "*, significantly different from B7-H1/614mel + control antibody group". The cell line is 624mel everywhere else, including the Fig. 4d axis labels.
- p. 6 Fig. 4d legend
significantly different from B7-H1/614mel + control antibody group
- p. 6 Fig. 4 legend (d)
B7-H1/614mel + control antibody group
Judge's note: The p6 image confirms '614mel' in the legend, while the Fig. 4d x-axis reads 'Mock/624mel' and 'B7-H1/624mel'. No 614mel line is introduced anywhere in the paper.
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Typo Discussion, p6: "Neither costimulation or apoptosis of T cells in this system were blocked by PD-1Ig". The correlative construction should be 'Neither ... nor ...'.
- p. 6 Discussion
Neither costimulation or apoptosis of T cells in
Judge's note: The page image shows the 'Neither ... or' construction exactly as quoted. This is a grammatical slip only.
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Typo Methods, Mouse studies, p7: "RAG-1–/– mice (H-2b) mice were inoculated". The word 'mice' is duplicated.
- p. 7 Methods, Mouse studies
mice (H-2b) mice were inoculated
- p. 7 Mouse studies
RAG-1–/– mice (H-2b) mice were inoculated
Judge's note: The page image shows 'mice' printed twice in this noun phrase.
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Typo Methods, p7: "at 4 × 10^5 per well were precoated cultured in plates precoated with 0.5 µg/ml". The first 'precoated' is spurious.
- p. 7 Methods, polyclonal T-cell apoptosis
were precoated cultured in plates precoated
- p. 7 Methods, apoptosis assays
were precoated cultured in plates precoated with
Judge's note: The page image shows the garbled phrase exactly as quoted, with 'precoated' printed twice.
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Typo Fig. 5c legend, p7: "Mock/P815 or B7-H1/P815 tumor cell sat1 × 10^5" should read 'tumor cells at 1 × 10^5'.
- p. 7 Fig. 5c legend
tumor cell sat1
Judge's note: The page image shows 'cell sat1' with the misplaced space, so this is in the printed page and is not an extraction artefact.
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Typo Reference 36, p8: "Finger, L.R. et al. G The human PD-1 gene". There is a stray 'G' before the title.
- p. 8 Reference 36
Finger, L.R. et al. G The human PD-1 gene
Judge's note: The page image shows the stray 'G' between 'et al.' and the title.
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Typo Reference 22, p8: "Georgescu, L., Vakkalanka, R.K. Elkon, K.B. & Crow, M.K.". The comma between 'R.K.' and 'Elkon' is missing.
- p. 8 Reference 22
Vakkalanka, R.K. Elkon, K.B.
Judge's note: The page image confirms there is no separator between the two authors' names.
Second check: none (judge only)