Advertisement

The Great Escape

In the movie The Great Escape, “problem” prisoners with multiple escape attempts are put in an “escape-proof” POW camp, where they use their cleverness and specialized skills to outwit their captors. However, when it comes to escaping, even Steve McQueen doesn’t have anything on cancer cells. Although human cancers express tumor antigens recognized by the immune system, host immune responses often fail to control tumor growth. Taube et al. now explain one way in which tumor cells may adapt to escape from immune surveillance.
The researchers found a strong association between expression of the immune-inhibitory molecule B7-H1 (PD-L1) on melanocytes and immune cell infiltration into tumors in patients with different stages of melanoma. The B7-H1+ melanocytes were found directly adjacent to the immune cells, with interferon-γ detected at the melanocyte–immune cell interface. Interferon-γ, which is secreted by the immune cells, induces B7-H1 expression; thus, the tumor may adapt by causing immune cells to trigger their own inhibition. Indeed, patients with B7-H1+ metastatic melanoma had prolonged overall survival when compared with B7-H1 metastatic melanoma patients, perhaps suggesting that B7-H1 expression by the tumors is stimulated by a more successful immune response. It remains to be seen whether blocking B7-H1 in these patients will further improve survival. But it is clear that for both prisoners and tumors, adaptation is the key to escape.

Abstract

Although many human cancers such as melanoma express tumor antigens recognized by T cells, host immune responses often fail to control tumor growth for as yet unexplained reasons. Here, we found a strong association between melanocyte expression of B7-H1 (PD-L1), an immune-inhibitory molecule, and the presence of tumor-infiltrating lymphocytes (TILs) in human melanocytic lesions: 98% of B7-H1+ tumors were associated with TILs compared with only 28% of B7-H1 tumors. Indeed, B7-H1+ melanocytes were almost always localized immediately adjacent to TILs. B7-H1/TIL colocalization was identified not only in melanomas but also in inflamed benign nevi, indicating that B7-H1 expression may represent a host response to tissue inflammation. Interferon-γ, a primary inducer of B7-H1 expression, was detected at the interface of B7-H1+ tumors and TILs, whereas none was found in B7-H1 tumors. Therefore, TILs may actually trigger their own inhibition by secreting cytokines that drive tumor B7-H1 expression. Consistent with this hypothesis, overall survival of patients with B7-H1+ metastatic melanoma was significantly prolonged compared with that of patients with B7-H1 metastatic melanoma. Therefore, induction of the B7-H1/PD-1 pathway may represent an adaptive immune resistance mechanism exerted by tumor cells in response to endogenous antitumor activity and may explain how melanomas escape immune destruction despite endogenous antitumor immune responses. These observations suggest that therapies that block this pathway may benefit patients with B7-H1+ tumors.

Get full access to this article

View all available purchase options and get full access to this article.

Already a subscriber or AAAS Member? Log In

Supplementary Material

Summary

Materials and Methods
Fig. S1. Geographic patterns of CD3+ TILs corresponding to the patterns of B7-H1 expression in cases shown in Fig. 1.
Fig. S2. Immunohistochemical characterization of cell types and architecture at the interface of B7-H1 expression and immune infiltrates in a melanoma lesion.
Fig. S3. Kinetics of B7-H1 induction by IFN-γ in cultured human melanoma cells.
Fig. S4. Comparison of B7-H1 detection in fresh and FFPE tissues using mAb 5H1.
Fig. S5. Comparison of B7-H1 detection by the mAb 5H1 versus the polyclonal antibody 4059.
Fig. S6. Comparative specificities of anti–B7-H1 mAb 5H1 and polyclonal antibody 4059 by Western blotting.
Fig. S7. B7-H1+ tumor and associated TILs sampled by laser capture microdissection.
Table S1. B7-H1 expression by melanocytes and infiltrating immune cells in 54 in situ and invasive primary melanomas does not correlate with pT or TNM stage.

Resources

File (4-127ra37_sm.pdf)

References and Notes

1
Benlalam H., Labarrière N., Linard B., Derré L., Diez E., Pandolfino M. C., Bonneville M., Jotereau F., Comprehensive analysis of the frequency of recognition of melanoma-associated antigen (MAA) by CD8 melanoma infiltrating lymphocytes (TIL): Implications for immunotherapy. Eur. J. Immunol. 31, 2007–2015 (2001).
2
Kamposioras K., Pentheroudakis G., Pectasides D., Pavlidis N., Malignant melanoma of unknown primary site. To make the long story short. A systematic review of the literature. Crit. Rev. Oncol. Hematol. 78, 112–126 (2011).
3
Zou W., Chen L., Inhibitory B7-family molecules in the tumour microenvironment. Nat. Rev. Immunol. 8, 467–477 (2008).
4
Ishida Y., Agata Y., Shibahara K., Honjo T., Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J. 11, 3887–3895 (1992).
5
Dong H., Strome S. E., Salomao D. R., Tamura H., Hirano F., Flies D. B., Roche P. C., Lu J., Zhu G., Tamada K., Lennon V. A., Celis E., Chen L., Tumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion. Nat. Med. 8, 793–800 (2002).
6
Dong H., Zhu G., Tamada K., Chen L., B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat. Med. 5, 1365–1369 (1999).
7
Freeman G. J., Long A. J., Iwai Y., Bourque K., Chernova T., Nishimura H., Fitz L. J., Malenkovich N., Okazaki T., Byrne M. C., Horton H. F., Fouser L., Carter L., Ling V., Bowman M. R., Carreno B. M., Collins M., Wood C. R., Honjo T., Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J. Exp. Med. 192, 1027–1034 (2000).
8
Iwai Y., Ishida M., Tanaka Y., Okazaki T., Honjo T., Minato N., Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc. Natl. Acad. Sci. U.S.A. 99, 12293–12297 (2002).
9
Topalian S. T., Weiner G. J., Pardoll D. M., Cancer immunotherapy comes of age. J. Clin. Oncol. 29, 4828–4836 (2011).
10
Hodi F. S., O’Day S. J., McDermott D. F., Weber R. W., Sosman J. A., Haanen J. B., Gonzales R., Robert C., Schadendorf D., Hassel J. C., Akerly W., van den Eertwegh A. J., Lutzky J., Lorigan P., Vaubel J. M., Linette G. P., Hogg D., Ottensmeier C. H., Lebbé C., Peschel C., Quirt I., Clark J. I., Wolchok J. D., Weber J. S., Tian J., Yellin M. J., Nichol G. M., Hoos A., Urba W. J., Improved survival with ipilimumab in patients with metastatic melanoma. N. Engl. J. Med. 363, 711–723 (2010).
11
Robert C., Thomas L., Bondarenko I., O’Day S., M D J. W., Garbe C., Lebbe C., Baurain J. F., Testori A., Grob J. J., Davidson N., Richards J., Maio M., Hauschild A., Miller W. H., Gascon P., Lotem M., Harmankaya K., Ibrahim R., Francis S., Chen T. T., Humphrey R., Hoos A., Wolchok J. D., Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N. Engl. J. Med. 364, 2517–2526 (2011).
12
Downey S. G., Klapper J. A., Smith F. O., Yang J. C., Sherry R. M., Royal R. E., Kammula U. S., Hughes M. S., Allen T. E., Levy C. L., Yellin M., Nichol G., White D. E., Steinberg S. M., Rosenberg S. A., Prognostic factors related to clinical response in patients with metastatic melanoma treated by CTL-associated antigen-4 blockade. Clin. Cancer Res. 13, 6681–6688 (2007).
13
Beck K. E., Blansfield J. A., Tran K. Q., Feldman A. L., Hughes M. S., Royal R. E., Kammula U. S., Topalian S. L., Sherry R. M., Kleiner D., Quezado M., Lowy I., Yellin M., Rosenberg S. A., Yang J. C., Enterocolitis in patients with cancer after antibody blockade of cytotoxic T-lymphocyte–associated antigen 4. J. Clin. Oncol. 24, 2283–2289 (2006).
14
Waterhouse P., Penninger J. M., Timms E., Wakeham A., Shahinian A., Lee K. P., Thompson C. B., Griesser H., Mak T. W., Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science 270, 985–988 (1995).
15
Brown J. A., Dorfman D. M., Ma F. R., Sullivan E. L., Munoz O., Wood C. R., Greenfield E. A., Freeman G. J., Blockade of programmed death-1 ligands on dendritic cells enhances T cell activation and cytokine production. J. Immunol. 170, 1257–1266 (2003).
16
Liang S. C., Latchman Y. E., Buhlmann J. E., Tomczak M. F., Horwitz B. H., Freeman G. J., Sharpe A. H., Regulation of PD-1, PD-L1, and PD-L2 expression during normal and autoimmune responses. Eur. J. Immunol. 33, 2706–2716 (2003).
17
Yamazaki T., Akiba H., Iwai H., Expression of programmed death 1 ligands by murine T cells and APC. J. Immunol. 169, 5538–5545 (2002).
18
Curiel T. J., Wei S., Dong H., Alvarez X., Cheng P., Mottram P., Krzysiek R., Knutson K. L., Daniel B., Zimmermann M. C., David O., Burow M., Gordon A., Dhurandhar N., Myers L., Berggren R., Hemminki A., Alvarez R. D., Emilie D., Curiel D. T., Chen L., Zou W., Blockade of B7-H1 improves myeloid dendritic cell–mediated antitumor immunity. Nat. Med. 9, 562–567 (2003).
19
Butte M. J., Keir M. E., Phamduy T. B., Sharpe A. H., Freeman G. J., Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses. Immunity 27, 111–122 (2007).
20
Tivol E. A., Borriello F., Schweitzer A. N., Lynch W. P., Bluestone J. A., Sharpe A. H., Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity 3, 541–547 (1995).
21
Dong H., Zhu G., Tamada K., Flies D. B., van Deursen J. M., Chen L., B7-H1 determines accumulation and deletion of intrahepatic CD8+ T lymphocytes. Immunity 20, 327–336 (2004).
22
Nishimura H., Okazaki T., Tanaka Y., Nakatani K., Hara M., Matsumori A., Sasayama S., Mizoguchi A., Hiai H., Minato N., Honjo T., Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science 291, 319–322 (2011).
23
Flies D. B., Chen L., The new B7s: Playing a pivotal role in tumor immunity. J. Immunother. 30, 251–260 (2007).
24
Wu C., Zhu Y., Jiang J., Zhao J., Zhang X. G., Xu N., Immunohistochemical localization of programmed death-1 ligand-1 (PD-L1) in gastric carcinoma and its clinical significance. Acta Histochem. 108, 19–24 (2006).
25
Ohigashi Y., Sho M., Yamada Y., Tsurui Y., Hamada K., Ikeda N., Mizuno T., Yoriki R., Kashizuka H., Yane K., Tsushima F., Otsuki N., Yagita H., Azuma M., Nakajima Y., Clinical significance of programmed death-1 ligand-1 and programmed death-1 ligand-2 expression in human esophageal cancer. Clin. Cancer Res. 11, 2947–2953 (2005).
26
Thompson R. H., Kuntz S. M., Leibovich B. C., Dong H., Lohse C. M., Webster W. S., Tumor B7-H1 is associated with poor prognosis in renal cell carcinoma patients with long-term follow-up. Cancer Res. 66, 3381–3385 (2006).
27
Thompson R. H., Gillett M. D., Cheville J. C., Lohse C. M., Dong H., Webster W. S., Krejci K. G., Lobo J. R., Sengupta S., Chen L., Zincke H., Blute M. L., Strome S. E., Leibovich B. C., Kwon E. D., Costimulatory B7-H1 in renal cell carcinoma patients: Indicator of tumor aggressiveness and potential therapeutic target. Proc. Natl. Acad. Sci. U.S.A. 101, 17174–17179 (2004).
28
Ghebeh H., Mohammed S., Al-Omair A., Qattan A., Lehe C., Al-Qudaihi G., Elkum N., Alshabanah M., Bin Amer S., Tulbah A., Ajarim D., Al-Tweigeri T., Dermime S., The B7-H1 (PD-L1) T lymphocyte-inhibitory molecule is expressed in breast cancer patients with infiltrating ductal carcinoma: Correlation with important high-risk prognostic factors. Neoplasia 8, 190–198 (2006).
29
Brahmer J. R., Drake C. G., Wollner I., Powderly J. D., Picus J., Sharfman W. H., Stankevich E., Pons A., Salay T. M., McMiller T. L., Gilson M. M., Wang C., Selby M., Taube J. M., Anders R., Chen L., Korman A. J., Pardoll D. M., Lowy I., Topalian S. L., Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: Safety, clinical activity, pharmacodynamics, and immunologic correlates. J. Clin. Oncol. 28, 3167–3175 (2010).
30
Thompson R. H., Dong H., Kwon E. D., Implications of B7-H1 expression in clear cell carcinoma of the kidney for prognostication and therapy. Clin. Cancer Res. 13, 709s–715s (2007).
31
Schrieber R. D., Old L. J., Smyth M. J., Cancer immunoediting: Integrating immunity’s roles in cancer suppression and promotion. Science 331, 1565–1570 (2011).
32
Dunn G. P., Bruce A. T., Ikeda H., Old L. J., Schreiber R. D., Cancer immunoediting: From immunosurveillance to tumor escape. Nat. Immunol. 3, 991–998 (2002).
33
Parsa A. T., Waldron J. S., Panner A., Crane C. A., Parney I. F., Barry J. J., Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma. Nat. Med. 13, 84–88 (2007).
34
Wölfle S. J., Strebovsky J., Bartz H., Sähr A., Arnold C., Kaiser C., Dalpke A. H., Heeg K., PD-L1 expression on tolerogenic APCs is controlled by STAT-3. Eur. J. Immunol. 41, 413–424 (2011).
35
Kinter A. L., Godbout E. J., McNally J. P., Sereti I., Roby G. A., O’Shea M. A., Fauci A. S., The common γ-chain cytokines IL-2, IL-7, IL-15, and IL-21 induce the expression of programmed death-1 and its ligands. J. Immunol. 181, 6738–6746 (2008).
36
Karim R., Jordanova E. S., Piersma S. J., Kenter G. G., Chen L., Boer J. M., Melief C. J., van der Burg S. H., Tumor-expressed B7-H1 and B7-DC in relation to PD-1+ T-cell infiltration and survival of patients with cervical carcinoma. Clin. Cancer Res. 15, 6341–6347 (2009).
37
Gajewski T. F., Louahed J., Brichard V. G., Gene signature in melanoma associated with clinical activity: A potential clue to unlock cancer immunotherapy. Cancer J. 16, 399–403 (2010).
38
Ji R. R., Chasalow S. D., Wang L., Hamid O., Schmidt H., Cogswell J., Alaparthy S., Berman D., Jure-Kunkel M., Siemers N. O., Jackson J. R., Shahabi V., An immune-active tumor microenvironment favors clinical response to ipilimumab. Cancer Immunol. Immunother. 10.1007/s00262-011-1172-6 (2011).
39
Sznol M., Powderly J. D., Smith D. C., Brahmer J. R., Drake C. G., McDermott D. F., Lawrence D. P., Wolchok J. D., Topalian S. L., Lowy I., Safety and antitumor activity of biweekly MDX-1106 (anti-PD-1, BMS-936558/ONO-4538) in patients with advanced refractory malignancies [abstract 2506]. J. Clin. Oncol. (Meet. Abstr.) 28, 15s (2010).
40
Zhang L., Conejo-Garcia J. R., Katsaros D., Gimotty P. A., Massobrio M., Regnani G., Makrigiannakis A., Gray H., Schlienger K., Liebman M. N., Rubin S. C., Coukos G., Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N. Engl. J. Med. 348, 203–213 (2003).
41
Fukunaga A., Miyamoto M., Cho Y., Murakami S., Kawarada Y., Oshikiri T., Kato K., Kurokawa T., Suzuoki M., Nakakubo Y., Hiraoka K., Itoh T., Morikawa T., Okushiba S., Kondo S., Katoh H., CD8+ tumor-infiltrating lymphocytes together with CD4+ tumor-infiltrating lymphocytes and dendritic cells improve the prognosis of patients with pancreatic adenocarcinoma. Pancreas 28, e26–e31 (2004).
42
Eerola A. K., Soini Y., Pääkkö P., A high number of tumor-infiltrating lymphocytes are associated with a small tumor size, low tumor stage, and a favorable prognosis in operated small cell lung carcinoma. Clin. Cancer Res. 6, 1875–1881 (2000).
43
Schumacher K., Haensch W., Röefzaad C., Schlag P. M., Prognostic significance of activated CD8+ T cell infiltrations within esophageal carcinomas. Cancer Res. 61, 3932–3936 (2001).
44
Pagès F., Berger A., Camus M., Sanchez-Cabo F., Costes A., Molidor R., Mlecnik B., Kirilovsky A., Nilsson M., Damotte D., Meatchi T., Bruneval P., Cugnenc P. H., Trajanoski Z., Fridman W. H., Galon J., Effector memory T cells, early metastasis, and survival in colorectal cancer. N. Engl. J. Med. 353, 2654–2666 (2005).
45
Webster W. S., Lohse C. M., Thompson R. H., Dong H., Frigola X., Dicks D. L., Sengupta S., Frank I., Leibovich B. C., Blute M. L., Cheville J. C., Kwon E. D., Mononuclear cell infiltration in clear-cell renal cell carcinoma independently predicts patient survival. Cancer 107, 46–53 (2006).
46
Galon J., Costes A., Sanchez-Cabo F., Kirilovsky A., Mlecnik B., Lagorce-Pagès C., Tosolini M., Camus M., Berger A., Wind P., Zinzindohoué F., Bruneval P., Cugnenc P. H., Trajanoski Z., Fridman W. H., Pagès F., Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 313, 1960–1964 (2006).
47
Clemente C. G., Mihm M. C., Bufalino R., Zurrida S., Collini P., Cascinelli N., Prognostic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma. Cancer 77, 1303–1310 (1996).
48
Mihm M. C., Clemente C. G., Cascinelli N., Tumor infiltrating lymphocytes in lymph node melanoma metastases: A histopathologic prognostic indicator and an expression of local immune response. Lab. Invest. 74, 43–47 (1996).
49
Hino R., Kabashima K., Kato Y., Yagi H., Nakamura M., Honjo T., Okazaki T., Tokura Y., Tumor cell expression of programmed cell death-1 ligand 1 is a prognostic factor for malignant melanoma. Cancer 116, 1757–1766 (2010).
50
Gadiot J., Hooijkaas A. I., Kaiser A. D. M., van Tinteren H., van Boven H., Blank C., Overall survival and PD-L1 expression in metastasized malignant melanoma. Cancer 117, 2192–2201 (2011).
51
Curtin J. A., Fridlyand J., Kageshita T., Patel H. N., Busam K. J., Kutzner H., Cho K. H., Aiba S., Bröcker E. B., LeBoit P. E., Pinkel D., Bastian B. C., Distinct sets of genetic alterations in melanoma. N. Engl. J. Med. 353, 2135–2147 (2005).
52
Curtin J. A., Busam K., Pinkel D., Bastian B. C., Somatic activation of KIT in distinct subtypes of melanoma. J. Clin. Oncol. 24, 4340–4346 (2006).
53
Balch C. M., Gershenwald J. E., Soong S. J., Thompson J. F., Atkins M. B., Byrd D. R., Buzaid A. C., Cochran A. J., Coit D. G., Ding S., Eggermont A. M., Flaherty K. T., Gimotty P. A., Kirkwood J. M., McMasters K. M., Mihm M. C., Morton D. L., Ross M. I., Sober A. J., Sondak V. K., Final version of 2009 AJCC melanoma staging and classification. J. Clin. Oncol. 27, 6199–6206 (2009).

Information & Authors

Information

Published In

Science Translational Medicine
Volume 4 | Issue 127
March 2012

Submission history

Received: 9 January 2012
Accepted: 23 February 2012

Permissions

Request permissions for this article.

Acknowledgments

We thank R. Li, C. Umbricht, Y. Liu, and F. Housseau for helpful discussions, as well as J. Califano and J. Handa for their support (all Johns Hopkins University School of Medicine). Funding: This study was supported by grants from the National Cancer Institute (CA016359, CA97085, and CA85721 to L.C.), the NIH (R01DK080736 and R01DK081417 to R.A.A.), the Melanoma Research Alliance (to D.M.P., S.L.T., and L.C.), the Barney Family Foundation (to S.L.T.), the Michael Rolfe Foundation for Pancreatic Cancer Research (to R.A.A.), and the Dermatology Foundation (to J.M.T.). Author contributions: J.M.T., R.A.A., G.D.Y., S.C., D.M.P., S.L.T., and L.C. conceived and designed the experiments. J.M.T., R.A.A., G.D.Y., H.X., R.S., T.L.M., and S.C. performed the experiments. J.M.T., R.A.A., G.D.Y., T.L.M., S.C., A.P.K., D.M.P., S.L.T., and L.C. analyzed the data. J.M.T., D.M.P., S.L.T., and L.C. wrote the manuscript. Competing interests: S.L.T. is a consultant to (uncompensated) and S.L.T., J.M.T., R.A.A., and H.X. receive research support from Bristol-Myers Squibb. The 5H1 antibody (made in L.C.’s laboratory, U.S. 7,797,710 and U.S. 7,892,540) will be distributed via a standard University Material Transfer Agreements for research, which is consistent with Science Translational Medicine’s material sharing policy. The other authors declare that they have no competing interests.

Authors

Affiliations

Janis M. Taube* [email protected]
Department of Dermatology, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
Robert A. Anders
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
Geoffrey D. Young
Department of Otolaryngology, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
Haiying Xu
Department of Dermatology, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
Rajni Sharma
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
Tracee L. McMiller
Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
Shuming Chen
Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
Alison P. Klein
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
Drew M. Pardoll
Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
Suzanne L. Topalian* [email protected]
Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
Lieping Chen* [email protected]
Department of Dermatology, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
Department of Immunobiology, Yale University, New Haven, CT 06519, USA.

Notes

*
To whom correspondence should be addressed. E-mail: [email protected] (J.M.T.); [email protected] (S.L.T.); [email protected] (L.C.)

Metrics & Citations

Metrics

Article Usage
Altmetrics

Citations

Export citation

Select the format you want to export the citation of this publication.

Cited by

  1. Endocrinopathies Associated With Immune Checkpoint Inhibitors, Endocrine Emergencies, (301-314), (2022).https://doi.org/10.1016/B978-0-323-76097-3.00024-7
    Crossref
  2. Extracellular vesicles, tumor growth, and the metastatic process, Bone Cancer, (275-284), (2022).https://doi.org/10.1016/B978-0-12-821666-8.00058-X
    Crossref
  3. Analysis of multispectral imaging with the AstroPath platform informs efficacy of PD-1 blockade, Science, 372, 6547, (2021)./doi/10.1126/science.aba2609
    Abstract
  4. Blockade of the CD93 pathway normalizes tumor vasculature to facilitate drug delivery and immunotherapy, Science Translational Medicine, 13, 604, (2021)./doi/10.1126/scitranslmed.abc8922
    Abstract
  5. Spatially Resolved and Quantitative Analysis of the Immunological Landscape in Human Meningiomas, Journal of Neuropathology & Experimental Neurology, 80, 2, (150-159), (2021).https://doi.org/10.1093/jnen/nlaa152
    Crossref
  6. Comprehensive analysis of immune-related prognostic genes in the tumour microenvironment of hepatocellular carcinoma, BMC Cancer, 21, 1, (2021).https://doi.org/10.1186/s12885-021-08052-8
    Crossref
  7. Immunotyping in tubo‐ovarian high‐grade serous carcinoma by PD‐L1 and CD8+ T‐lymphocytes predicts disease‐free survival, APMIS, 129, 5, (254-264), (2021).https://doi.org/10.1111/apm.13116
    Crossref
  8. The inflammatory tumor microenvironment and tumor cell plasticity in the pathogenesis of colorectal cancer, Onkologiya. Zhurnal imeni P.A.Gertsena, 10, 4, (66), (2021).https://doi.org/10.17116/onkolog20211004166
    Crossref
  9. Potential predictive value of change in inflammatory cytokines levels subsequent to initiation of immune checkpoint inhibitor in patients with advanced non-small cell lung cancer, Cytokine, 138, (155363), (2021).https://doi.org/10.1016/j.cyto.2020.155363
    Crossref
  10. Cancer immunotherapy: Classification, therapeutic mechanisms, and nanomaterial-based synergistic therapy, Applied Materials Today, 24, (101149), (2021).https://doi.org/10.1016/j.apmt.2021.101149
    Crossref
  11. See more
Loading...

View Options

Get Access

Log in to view the full text

AAAS ID LOGIN

AAAS login provides access to Science for AAAS Members, and access to other journals in the Science family to users who have purchased individual subscriptions.

Log in via OpenAthens.
Log in via Shibboleth.

More options

Register for free to read this article

As a service to the community, this article is available for free. Login or register for free to read this article.

View options

PDF format

Download this article as a PDF file

Download PDF

Media

Figures

Multimedia

Tables

Share

Share

Share article link

Share on social media