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Prognostic Significance of Primary Tumor-Infiltrating Lymphocytes in a Contemporary Melanoma Cohort

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Abstract

Background

The prognostic impact of tumor-infiltrating lymphocytes (TILs) on outcomes and treatment efficacy for patients with melanoma in the contemporary era remains poorly characterized.

Methods

Consecutive patients who underwent wide excision and sentinel lymph node biopsy for cutaneous melanoma 1 mm thick or thicker at a single institution were identified (2006–2019). The patients were stratified based on primary tumor TIL status as brisk (bTILs), non-brisk (nbTILs), or absent (aTILs). Associations between patient factors and outcomes were analyzed using multivariable analysis.

Results

Of the 1017 patients evaluated, 846 (83.2 %) had primary TILs [nbTILs (n = 759, 89.7 %) and bTILs (n = 87, 10.3 %)]. In the multivariable analysis, the patients with any type of TILs had higher rates of regression [odds ratio (OR), 1.86; p = 0.016], lower rates of acral lentiginous histology (OR, 0.22; p < 0.001), and lower rates of SLN positivity (OR, 0.64; p = 0.042) than those without TILs. The multivariable analysis found no association between disease-specific survival and bTILs [hazard ratio (HR), 1.04; p = 0.927] or nbTILs (HR, 0.89; p = 0.683). An association was found between bTILs and recurrence-free survival (RFS) advantage [bTILs (HR 0.46; p = 0.047), nbTILs (HR 0.71; p = 0.088)], with 5-year RFS rates of 84 % for bTILs, 71.8 % for nbTILs, and 68.4 % for aTILs (p = 0.044). For the 114 immune checkpoint blockade (ICB)-naïve patients who experienced a recurrence treated with ICB therapy, no association was observed between progression-free survival and bTILs (HR, 0.64; p = 0.482) or nbTILs (HR, 0.58; p = 0.176).

Conclusions

The prognostic significance of primary TILs in the contemporary melanoma era appears complex. Further studies characterizing the phenotype of TILs and their association with regional metastasis and responsiveness to ICB therapy are warranted.

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Author notes

  1. Richard J. Straker III and Katharine Krupp have Contributed equally to this study as primary authors.

Authors and Affiliations

  1. Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Richard J. Straker III MD, Katharine Krupp BA, Cimarron E. Sharon MD, Alexandra S. Thaler BA, Nicholas J. Kelly BA, John T. Miura MD & Giorgos C. Karakousis MD

  2. Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Emily Y. Chu MD, PhD

  3. Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    David E. Elder MBChB & Xiaowei Xu MD, PhD

  4. Hospital of the University of Pennsylvania, 4 Maloney, 3400 Spruce Street, Philadelphia, PA, 19104, USA

    Richard J. Straker III MD

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Contributions

Substantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data: RJS, KK, CES, AST, NJK, EYC, DEE, XX, JTM, GCK. Drafting the article or revising it critically for important intellectual content: RJS, KK, CES, AST, NJK, EYC, DEE, XX, JTM, GCK. Final approval of the version to be published: RJS, KK, CES, AST, NJK, EYC, DEE, XX, JTM, GCK. All authors have reviewed and approved the submitted manuscript, and agree to be accountable for all aspects of the work submitted.

Corresponding author

Correspondence to Richard J. Straker III MD.

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Reviewed and approved by the University of Pennsylvania (protocol #: 850510).

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Straker, R.J., Krupp, K., Sharon, C.E. et al. Prognostic Significance of Primary Tumor-Infiltrating Lymphocytes in a Contemporary Melanoma Cohort. Ann Surg Oncol 29, 5207–5216 (2022). https://doi.org/10.1245/s10434-022-11478-4

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