Intratumoral PD1<sup>+</sup>CD38<sup>+</sup>Tim3<sup>+</sup> CD8<sup>+</sup> T Cells in Pre-BCG Tumor Tissues Are Associated with Poor Responsiveness to BCG Immunotherapy in Patients with Non-Muscle Invasive Bladder Cancer
Debashree Basak,
Soumya Mondal,
Swadeep Kumar Srivastava,
Deborpita Sarkar,
Ishita Sarkar,
Sukanya Basu,
Arpita Bhoumik,
Snehanshu Chowdhury,
Dilip Kumar Pal,
Shilpak Chatterjee
Affiliations
Debashree Basak
Division of Cancer Biology and Inflammatory Disorder, IICB-Translational Research Unit of Excellence, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, India
Soumya Mondal
Department of Urology, IPGME&R and SSKM Hospital, Kolkata 700020, India
Swadeep Kumar Srivastava
Department of Urology, IPGME&R and SSKM Hospital, Kolkata 700020, India
Deborpita Sarkar
Division of Cancer Biology and Inflammatory Disorder, IICB-Translational Research Unit of Excellence, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, India
Ishita Sarkar
Division of Cancer Biology and Inflammatory Disorder, IICB-Translational Research Unit of Excellence, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, India
Sukanya Basu
Division of Cancer Biology and Inflammatory Disorder, IICB-Translational Research Unit of Excellence, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, India
Arpita Bhoumik
Division of Cancer Biology and Inflammatory Disorder, IICB-Translational Research Unit of Excellence, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, India
Snehanshu Chowdhury
Division of Cancer Biology and Inflammatory Disorder, IICB-Translational Research Unit of Excellence, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, India
Dilip Kumar Pal
Department of Urology, IPGME&R and SSKM Hospital, Kolkata 700020, India
Shilpak Chatterjee
Division of Cancer Biology and Inflammatory Disorder, IICB-Translational Research Unit of Excellence, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, India
Intravesical immunotherapy with Bacillus Calmette–Guerin (BCG) is a standard of care therapy for non-muscle invasive bladder cancer (NMIBC), which accounts for about 75% of newly diagnosed urothelial cancer. However, given the frequent recurrence and progression, identification of a pre-treatment biomarker capable of predicting responsiveness to BCG in NMIBC is of utmost importance. Herein, using multiparametric flow cytometry, we characterized CD8+ T cells from peripheral blood and tumor tissues collected from 27 pre-BCG patients bearing NMIBC to obtain immune correlates of bladder cancer prognosis and responsiveness to BCG therapy. We observed that intratumoral CD8+ T cell subsets were highly heterogenous in terms of their differentiation state and exist at different proportions in tumor tissues. Remarkably, among the different CD8+ T cell subsets present in the tumor tissues, the frequency of the terminally exhausted-like CD8+ T cell subset, marked as PD1+CD38+Tim3+ CD8+ T cells, was inversely correlated with a favorable outcome for patients and a responsiveness to BCG therapy. Moreover, we also noted that the intratumoral abundance of the progenitor exhausted-like PD1+CD8+ T cell subset in pre-BCG NMIBC tumor tissues was indicative of better recurrence-free survival after BCG. Collectively, our study led to the identification of biomarkers that can predict the therapeutic responsiveness of BCG in NMIBC.