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Table of Contents
LETTER TO THE EDITOR
Year : 2019  |  Volume : 27  |  Issue : 1  |  Page : 39-40

Role of tumor-infiltrating lymphocytes in melanoma


Department of Radiation Oncology, Kayseri Education and Research Hospital, Kayseri, Turkey

Date of Web Publication4-Jan-2019

Correspondence Address:
Dr. Yasemin Benderli Cihan
Department of Radiation Oncology, Kayseri Education and Research Hospital, 38010 Kayseri
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/tjps.tjps_49_18

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How to cite this article:
Cihan YB. Role of tumor-infiltrating lymphocytes in melanoma. Turk J Plast Surg 2019;27:39-40

How to cite this URL:
Cihan YB. Role of tumor-infiltrating lymphocytes in melanoma. Turk J Plast Surg [serial online] 2019 [cited 2019 Nov 13];27:39-40. Available from: http://www.turkjplastsurg.org/text.asp?2019/27/1/39/249402



It has been more than a century after recognition of various numbers of lymphocytes in malignant tumors. These lymphocytes were termed as tumor-infiltrating lymphocytes (TILs). Initially, it was thought that the TILs indicate chronic infiltration in cancer; however, then, the question whether they comprise a media for cancer proliferation or they occur as a host response against cancer was discussed.[1] In recent years, importance of TILs has been revealed in many solid tumors such as melanoma, renal cell carcinoma, breast cancer, and lung cancer.[1],[2],[3],[4],[5] The TILs include specific B-cells, natural killers, adaptive immune effector, and immunosuppressive cells, which are responsible for killing tumor cells and tumor regression. It is known that lymphocyte subsets play immunoregulatory role in neoplasm. The antigen-specific effector response that induces immune response is generated by T-lymphocytes. A well-functioning immune system is required to operate host defense mechanisms against tumors. T-lymphocytes are major cells playing a role for the generation of effective immune response against tumor.[2],[3],[4]

There are studies investigated prognostic value of type and grade of TIL in various tumors. It was found that tumor prognosis is negatively correlated to lymphocytic infiltration surrounding tumor.[2] In previous studies, it has been proven that infiltration of tumor by lymphocytes is associated to better prognosis in breast, ovarian, and colon cancers.[3] In the Boston Collaborates of Melanoma Study showed that melanoma cases infiltrated by intense lymphocytes had better prognosis.[2] In their study, Thomas et al. assessed TILs in 2845 patients with invasive melanoma who were diagnosed between 1998 and 2003. Authors found that mortality rate was decreased by 30% in patients with mild lymphocyte infiltration and by 50% in those with intense lymphocyte infiltration.[3]

The finding that lymphoid response is less frequently observed in metastatic diseases when compared to primary disease has attracted attention in this issue. It is still being investigated whether TILs around malignant melanoma could be a predictor for treatment with monoclonal antibodies which inhibit checkpoints of immune system.[1],[4] Tumeh et al. emphasized predictive value of CD8 T-cells at tumor margin of metastasis from melanoma in the assessment of response to treatment.[5] In the study by Diem et al., it was evaluated whether there is a correlation between T-cell infiltration and response to ipilimumab after progression of Stage IV in lymph node metastasis on Stage III melanoma. Authors suggested that median progression-free and overall survival showed a tendency favoring patients with TIL-enriched lymph node metastasis (6.8 vs. 3.3 months; P = 0.09), concluding presence of a correlation.[6] In another study, ipilimumab caused upregulation of CD4+ and CD8+ TILs by an inducible factor in patients with melanoma. In the same study, it was suggested that the decrease in the proportion of CD8+ effector T-cells was associated to recurrence.[7]

In conclusion, the lymphocytic response around tumor can be a marker for immunological response; however, immunological response may be facilitative for tumor development as well. Identification quantitative measurement of lymphocyte subtypes may be important to determine prognostic and predictive value of lymphocytic infiltration. In the future, designing studies for investigation of specific marker expression in TILs and elucidation of inhibitory mechanisms which taking antigen specificity into account will allow developing treatment strategies. Further studies are needed in this field.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Lee N, Zakka LR, Mihm MC Jr., Schatton T. Tumour-infiltrating lymphocytes in melanoma prognosis and cancer immunotherapy. Pathology 2016;48:177-87.  Back to cited text no. 1
    
2.
Weiss SA, Han SW, Lui K, Tchack J, Shapiro R, Berman R, et al. Immunologic heterogeneity of tumor-infiltrating lymphocyte composition in primary melanoma. Hum Pathol 2016;57:116-25.  Back to cited text no. 2
    
3.
Thomas NE, Busam KJ, From L, Kricker A, Armstrong BK, Anton-Culver H, et al. Tumor-infiltrating lymphocyte grade in primary melanomas is independently associated with melanoma-specific survival in the population-based genes, environment and melanoma study. J Clin Oncol 2013;31:4252-9.  Back to cited text no. 3
    
4.
Ji RR, Chasalow SD, Wang L, Hamid O, Schmidt H, Cogswell J, et al. An immune-active tumor microenvironment favors clinical response to ipilimumab. Cancer Immunol Immunother 2012;61:1019-31.  Back to cited text no. 4
    
5.
Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, Robert L, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 2014;515:568-71.  Back to cited text no. 5
    
6.
Diem S, Hasan Ali O, Ackermann CJ, Bomze D, Koelzer VH, Jochum W, et al. Tumor infiltrating lymphocytes in lymph node metastases of stage III melanoma correspond to response and survival in nine patients treated with ipilimumab at the time of stage IV disease. Cancer Immunol Immunother 2018;67:39-45.  Back to cited text no. 6
    
7.
Wang W, Yu D, Sarnaik AA, Yu B, Hall M, Morelli D, et al. Biomarkers on melanoma patient T cells associated with ipilimumab treatment. J Transl Med 2012;10:146.  Back to cited text no. 7
    




 

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