Background: Penile cancer is a rare neoplasm worldwide. Despite a higher incidence in the Brazilian Northeast region, data regarding chemotherapy (CHT) treatment of penile cancer in Brazil is scarce. The relationship between markers of immunosuppression in the tumor microenvironment of penile cancer and MDSCs (Myeloid Derived Suppressor Cells) is still poorly understood. Methods: 294 patients affected by Squamous Penile Cancer treated at the Haroldo Juaçaba Hospital (Ceará-Brazil) between 2000 and 2021 (82 underwent chemotherapy: 27 adjuvant, 31 neoadjuvant and 24 palliative ) were retrospectively evaluated due to their clinical and histopathological characteristics and the following immunohistochemical markers: PD-L1, CD8t (intratumoral), CD163t (intratumoral), CD84, HLA-DR II. We sought to correlate these biomarkers to clinical staging, type (neoadjuvant, adjuvant or palliative) and response to CHT, PFS post-Chemotherapy (PFS-CHT), Overall Survival by stage (OS) and OS post-Chemotherapy (OS-CHT). Results: The median age for all patients was 62,9 years (18-103). Partial penile amputation was the most common surgery (74%), followed by inguinal lymphadenectomy (56%). Platinum Doublet was administered in 95% of cases. OS at 5 years for stages I, II, III e IV was 95,3%, 93,6%, 87,4% and 14,8%, respectively. The response rate (RECIST) (PR, SD and PD) in those who underwent Neoadjuvant CT was 29% 22% and 48%, while in the Palliative group was 5%, 11% and 82% respectively. Median OS-CHT was 49 months in the adjuvant, 21 months in neoadjuvant and 12 months in palliative group (p<0.001 adjuvant vs neoadjuvant/palliative); PFS-CHT was 11 months, 4 months and 1 month in the adjuvant, neoadjuvant and palliative group, respectively (p<0.001). In the neoadjuvant group, those who underwent surgery (70%) had a PFS-CHT of 6 months versus 2 months in those who were not operated (p<0.001). In univariate analysis, PFS-CHT was significantly higher in those who had lower expression of CD8t (9 vs 5 months; p=0.02), or CD163t (7 vs 5 months; p=0.043) or CD84 (7 vs 5 months; p =0.043). Conclusions: This is the largest retrospective study on chemotherapy and survival outcomes in Brazil. Patients who underwent surgery and adjuvant CHT had the best prognosis in terms of survival followed by those operated after neoadjuvant CHT. Lower expression CD163t, or CD84 (marker of MDSCs) or CD8t correlated with greater PFS-CHT. These data may help to understand the suppressive microenvironment in penile cancer and response to chemotherapy.