Immunotype and immunohistologic characteristics of tumor-infiltrating immune cells are associated with clinical outcome in metastatic melanoma - PubMed (original) (raw)
Immunotype and immunohistologic characteristics of tumor-infiltrating immune cells are associated with clinical outcome in metastatic melanoma
Gulsun Erdag et al. Cancer Res. 2012.
Abstract
Immune cells infiltrating the microenvironment of melanoma metastases may either limit or promote tumor progression, but the characteristics that distinguish these effects are obscure. In this study, we systematically evaluated the composition and organization of immune cells that infiltrated melanoma metastases in human patients. Three histologic patterns of immune cell infiltration were identified, designated immunotypes A, B, and C. Immunotype A was characterized by no immune cell infiltrate. Immunotype B was characterized by infiltration of immune cells limited only to regions proximal to intratumoral blood vessels. Immunotype C was characterized by a diffuse immune cell infiltrate throughout a metastatic tumor. These immunotypes represented 29%, 63%, and 8% of metastases with estimated median survival periods of 15, 23, and 130 months, respectively. Notably, from immunotypes A to C, there were increasing proportions of B cells and decreasing proportions of macrophages. Overall, the predominant immune cells were T cells (53%), B cell lineage cells (33%), and macrophages (13%), with natural killer and mature dendritic cells only rarely present. Whereas higher densities of CD8(+) T cells correlated best with survival, a higher density of CD45(+) leukocytes, T cells, and B cells also correlated with increased survival. Together, our findings reveal striking differences in the immune infiltrate in melanoma metastases in patients, suggesting microenvironmental differences in immune homing receptors and ligands that affect immune cell recruitment. These findings are important, not only by revealing how the immune microenvironment can affect outcomes but also because they reveal characteristics that may help improve individualized therapy for patients with metastatic melanoma.
Conflict of interest statement
Conflicts of interest related to this study: None.
Figures
Figure 1. Immunotypes
TMAs are stained with routine H&E (400x and 100x), immunostained with CD34 and CD45, and scored for immune cell density and location for immunotyping. Metastatic melanomas are characterized as “Immunotype A” when immune cell infiltrate is absent, “Immunotype B” when immune cell infiltrate is perivascular only, and “Immunotype C” when immune cells are infiltrating among tumor cells beyond the vessels.
Figure 2. Immunotype frequency, prognosis, and cellular composition
(A) The proportion of patients with each immunotype, in the first surgical specimen in the TMA, (B) Kaplan-Meier survival estimates for patients with each Immunotype, (C) Mean numbers of each immune cell subset, by Immunotype, and for all patients, (D) Proportion of mean total immune cells infiltrating tumor that are represented by each cell subset, by Immunotype.
Figure 3. Immune cell subsets overall and across patient groups
(A) Box plots of numbers of immune cell subsets, per mm2, in first melanoma metastases for 147 patients. Boxes represent 25th to 75th percentiles. Middle bar identifies median; solid circle represents mean; whiskers show minimum and maximum, (B) Percentages of tumor-infiltrating immune cells in pie chart, (C) Mean numbers of immune cell subsets for clinical subgroups. Numbers of tumors represented by each bar are shown below the graph (peritoneum = one), (D) Mean numbers of cells expressing FoxP3 or PD1 for clinical subgroups.
Figure 4. Patient survival and associations with immune cell density
Representative examples of sections with low- or high- numbers of cells staining for CD45, CD3, CD8, CD20, and CD138 are shown beside Kaplan-Meier survival curves for low and high counts of those markers. Magnification, 200×.
Similar articles
- [Prognostic value of tumor-infiltrating immune cells in melanoma].
Ladányi A. Ladányi A. Magy Onkol. 2013 Jun;57(2):85-95. Epub 2013 Apr 3. Magy Onkol. 2013. PMID: 23795353 Review. Hungarian. - Prognostic impact of B-cell density in cutaneous melanoma.
Ladányi A, Kiss J, Mohos A, Somlai B, Liszkay G, Gilde K, Fejös Z, Gaudi I, Dobos J, Tímár J. Ladányi A, et al. Cancer Immunol Immunother. 2011 Dec;60(12):1729-38. doi: 10.1007/s00262-011-1071-x. Epub 2011 Jul 21. Cancer Immunol Immunother. 2011. PMID: 21779876 Free PMC article. - Patterns of immune-cell infiltration in murine models of melanoma: roles of antigen and tissue site in creating inflamed tumors.
Leick KM, Pinczewski J, Mauldin IS, Young SJ, Deacon DH, Woods AN, Bosenberg MW, Engelhard VH, Slingluff CL Jr. Leick KM, et al. Cancer Immunol Immunother. 2019 Jul;68(7):1121-1132. doi: 10.1007/s00262-019-02345-5. Epub 2019 May 27. Cancer Immunol Immunother. 2019. PMID: 31134297 Free PMC article. - Leukocyte infiltration and tumor cell plasticity are parameters of aggressiveness in primary cutaneous melanoma.
Hillen F, Baeten CI, van de Winkel A, Creytens D, van der Schaft DW, Winnepenninckx V, Griffioen AW. Hillen F, et al. Cancer Immunol Immunother. 2008 Jan;57(1):97-106. doi: 10.1007/s00262-007-0353-9. Epub 2007 Jun 30. Cancer Immunol Immunother. 2008. PMID: 17602225 Free PMC article. - Characteristics of Tumor-Infiltrating Lymphocytes Prior to and During Immune Checkpoint Inhibitor Therapy.
Plesca I, Tunger A, Müller L, Wehner R, Lai X, Grimm MO, Rutella S, Bachmann M, Schmitz M. Plesca I, et al. Front Immunol. 2020 Mar 4;11:364. doi: 10.3389/fimmu.2020.00364. eCollection 2020. Front Immunol. 2020. PMID: 32194568 Free PMC article. Review.
Cited by
- Losartan rewires the tumor-immune microenvironment and suppresses IGF-1 to overcome resistance to chemo-immunotherapy in ovarian cancer.
Sun Y, Yin Z, Li S, Wu L, Zhang Y, Zhao Y, Gomes Dos Santos IL, Subudhi S, Lei P, Muzikansky A, Yuan Z, Rueda BR, Jain RK, Xu L. Sun Y, et al. Br J Cancer. 2024 Oct 5. doi: 10.1038/s41416-024-02863-9. Online ahead of print. Br J Cancer. 2024. PMID: 39369055 - DrugReSC: targeting disease-critical cell subpopulations with single-cell transcriptomic data for drug repurposing in cancer.
Liu C, Zhang Y, Liang Y, Zhang T, Wang G. Liu C, et al. Brief Bioinform. 2024 Sep 23;25(6):bbae490. doi: 10.1093/bib/bbae490. Brief Bioinform. 2024. PMID: 39350337 Free PMC article. - The Importance of Predictive Biomarkers and Their Correlation with the Response to Immunotherapy in Solid Tumors-Impact on Clinical Practice.
Mihaila RI, Gheorghe AS, Zob DL, Stanculeanu DL. Mihaila RI, et al. Biomedicines. 2024 Sep 22;12(9):2146. doi: 10.3390/biomedicines12092146. Biomedicines. 2024. PMID: 39335659 Free PMC article. Review. - Spatial colocalization and combined survival benefit of natural killer and CD8 T cells despite profound MHC class I loss in non-small cell lung cancer.
Wessel RE, Ageeb N, Obeid JM, Mauldin IS, Goundry KA, Hanson GF, Hossain M, Lehman C, Gentzler RD, Wages NA, Slingluff CL Jr, Bullock TNJ, Dolatshahi S, Brown MG. Wessel RE, et al. J Immunother Cancer. 2024 Sep 18;12(9):e009126. doi: 10.1136/jitc-2024-009126. J Immunother Cancer. 2024. PMID: 39299754 Free PMC article. - Dermatological Neoplastic Diseases Complicating Treatment with Monoclonal Antibodies for Multiple Sclerosis.
Bile F, Sparaco M, Ruocco E, Miele G, Maida E, Vele R, Mele D, Bonavita S, Lavorgna L. Bile F, et al. J Clin Med. 2024 Aug 29;13(17):5133. doi: 10.3390/jcm13175133. J Clin Med. 2024. PMID: 39274345 Free PMC article. Review.
References
- Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006;313:1960–1964. - PubMed
- Eerola AK, Soini Y, Paakko 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. 2000;6:1875–1881. - PubMed
- Zhang L, Conejo-Garcia JR, Katsaros D, Gimotty PA, Massobrio M, Regnani G, et al. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med. 2003;348:203–213. - PubMed
Publication types
MeSH terms
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
Miscellaneous