A. J. Sinnamon1, C. E. Sharon1, Y. Song1, M. G. Neuwirth1, D. E. Elder2, X. Xu2, D. L. Fraker1, P. A. Gimotty3, G. C. Karakousis1 1Hospital Of The University Of Pennsylvania,Endocrine And Oncologic Surgery,Philadelphia, PA, USA 2Hospital Of The University Of Pennsylvania,Pathology,Philadelphia, PA, USA 3University Of Pennsylvania,Biostatistics, Epidemiology And Informatics,Philadelphia, PA, USA
Introduction:
The immune response to melanoma, manifested locally by tumor-infiltrating lymphocytes (TILs), has gained increasing attention in the era of effective immunotherapies. Men and women are known to have varying patterns of immunity, yet gender-specific prognostic implications of TILs have not been explored.
Methods:
Patients with clinically localized primary melanoma ≥0.76mm who underwent sentinel lymph node (SLN) biopsy were identified within our institutional melanoma database. Association between TILs (categorized as absent, nonbrisk, and brisk) and SLN positivity was evaluated using logistic regression. The possibility of interaction between gender and TILs on the rate of SLN positivity was assessed using the Wald test. Overall survival estimates were obtained using the Kaplan-Meier method and Cox regression with separate analyses performed by gender.
Results:
Among 1,367 patients identified, 794 (58%) were men. TILs were brisk in 143 (10%) lesions, nonbrisk in 903 (66%), and absent in 321 (23%); this distribution did not vary by gender (p=0.71). Among men, SLN positivity rate was significantly associated with TILs (brisk 3.8%, nonbrisk 16.9%, absent 26.6%, p<0.001). In contrast, there was no significant relationship between TILs and SLN status in women (see figure; p=0.49). Significant interaction between brisk TILs and female gender on SLN status was identified (p=0.029). This interaction remained significant in multivariable analysis adjusting for clinicopathologic factors (p=0.043). Among men, presence of brisk TILs was associated with prolonged overall survival (brisk HR 0.43, p=0.038; nonbrisk HR 0.84, p=0.34). This association was no longer significant after adjustment for SLN status (brisk HR 0.72, p=0.42; nonbrisk HR 1.05, p=0.79). In contrast, no association between TILs status and overall survival was observed among women (brisk HR 0.97, p=0.95; nonbrisk HR 1.06, p=0.85).
Conclusion:
The negative prognostic implications of absent TILs on SLN status and thus on survival appear to be stronger among men than women. This may provide some basis for better melanoma-specific prognosis among women.
