Citation
Wolkow N, Lee NG, Emerick KS, Freitag SK, Kaufman HL, Miller DM, Chang H-Y P, Stagner AM. Locally advanced conjunctival squamous cell carcinoma not responsive to immune checkpoint inhibitor therapy: 3 cases and a literature review. Ophthalmic Plast Reconstr Surg. Published online January 12, 2026. doi:10.1097/IOP.0000000000003174.
Overview
Three patients with locally advanced conjunctival squamous cell carcinoma arising in the inferior fornix were treated with PD-1 blockade. All three experienced disease progression during immunotherapy and ultimately required orbital exenteration for local disease control.
Tumor mutational burden was low in all three tumors. When considered alongside 18 previously reported cases of invasive conjunctival SCC treated with immunotherapy, the findings suggest that tumors arising in the sun-protected inferior fornix or inferior palpebral conjunctiva may be biologically distinct from tumors arising on the bulbar conjunctiva and may be less likely to respond to immune checkpoint inhibition.
Anatomic site may provide a clinically meaningful clue to tumor biology. Inferior-forniceal and inferior-palpebral conjunctival SCC may have lower tumor mutational burden and a lower probability of response to immune checkpoint inhibition than tumors arising on the sun-exposed bulbar conjunctiva.
Case series
74-year-old man
Therapy: Cemiplimab, 4 cycles
Outcome: Progression requiring orbital exenteration
TMB: 1.2 mut/Mb
54-year-old woman
Therapy: Pembrolizumab, 3 cycles
Outcome: Progression requiring orbital exenteration
TMB: 8.1 mut/Mb
69-year-old woman
Therapy: Pembrolizumab, 2 cycles
Outcome: Progression requiring orbital exenteration
TMB: 7.1 mut/Mb
Findings from the literature
- Eighteen additional cases of invasive conjunctival SCC treated with immunotherapy were identified.
- Tumors from responders tended to have higher tumor mutational burden than tumors from nonresponders.
- Inferior-forniceal and inferior-palpebral tumors may represent a lower-TMB subgroup.
- Bulbar conjunctival tumors may have different ultraviolet exposure and immunogenicity.
- Careful patient selection remains important when considering PD-1 blockade for locally advanced conjunctival SCC.
Authors
Natalie Wolkow, Nahyoung G. Lee, Kevin S. Emerick, Suzanne K. Freitag, Howard L. Kaufman, David M. Miller, Han-Ying P. Chang, and Anna M. Stagner.